Academic journal
POPULARITY
241 episodes with Oncotarget
2 episodes with Oncotarget
3 episodes with Oncotarget
Listen to a blog summary of a trending research paper published in Volume 14 of Oncotarget: "Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels." ____________________________________________________ Dihydrolipoamide S-succinyltransferase (DLST) is a crucial gene/protein/enzyme involved in the oxidative phosphorylation (OXPHOS) pathway and cellular energy production. Recent studies have demonstrated that, in neuroblastoma and triple-negative breast cancer (TNBC), increased expression of DLST is associated with increased tumor aggression and a poor disease prognosis. Researchers also found that, in leukemia and TNBC cell lines, the knockdown of DLST leads to apoptosis. These findings suggest that neuroblastoma and TNBC may benefit from DLST-inhibiting cancer therapy. In light of this evidence, researchers Christina Kuhn, Myriam Boeschen, Manuel Philip, Torsten Schöneberg, Doreen Thor, and Susanne Horn from the University of Leipzig, University Duisburg-Essen and the German Cancer Consortium investigated approved drugs that target DLST-activated tumors. In their recent study, the team used data from the Genomics of Drug Sensitivity in Cancer (GDSC) project to identify new drug candidates for the treatment of DLST-activated tumors. On January 12, 2023, their research paper was published in Oncotarget's Volume 14, entitled, “Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels.” “With the advent of complex genetic datasets of roughly 1000 cell lines in the Cancer Cell Line Encyclopedia (CCLE) and on drug resistance in the Genomics of Drug Sensitivity in Cancer project (GDSC), analyses of drug sensitivity have become possible on a larger scale [6, 7].” Full blog - https://www.oncotarget.org/2023/01/19/researchers-identify-new-drug-candidates-to-treat-dlst-tumors/ DOI - https://doi.org/10.18632/oncotarget.28342 Correspondence to - Christina Kuhn - Christina.Kuhn@medizin.uni-leipzig.de Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28342 Keywords - neuroblastoma, drug sensitivity, drug resistance, drug repurposing, DLST About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ For media inquiries, please contact media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001.” Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. In this new study, researchers Xiaofan Li, Cristina Abrahams, Abigail Yu, Millicent Embry, Robert Henningsen, Venita DeAlmeida, Shannon Matheny, Toni Kline, Alice Yam, Ryan Stafford, Trevor Hallam, Mark Lupher, and Arturo Molina from Sutro Biopharma reported the results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. “In order to explore the potential of STRO-001 in NHL, in the present study we investigated CD74 expression in cell types found in bone marrow, evaluated its cytotoxicity in NHL cell lines, and assessed its antitumor efficacy and toxicity in xenograft models of NHL.” STRO-001 displayed nanomolar and sub-nanomolar cytotoxicity in 88% (15/17) of cancer cell lines tested. STRO-001 showed potent cytotoxicity on proliferating B cells while limited cytotoxicity was observed on naïve human B cells. A linear dose-response relationship was demonstrated in vivo for DLBCL models SU-DHL-6 and U2932. Tumor regression was induced at doses less than 5 mg/kg, while maximal activity with complete cures were observed starting at 10 mg/kg. In MCL Mino and Jeko-1 xenografts, STRO-001 starting at 3 mg/kg significantly prolonged survival or induced tumor regression, respectively, leading to tumor eradication in both models. “In summary, high CD74 expression levels in tumors, nanomolar cellular potency, and significant anti-tumor in DLBCL and MCL xenograft models support the ongoing clinical study of STRO-001 in patients with B-cell NHL.” DOI: https://doi.org/10.18632/oncotarget.28341 Correspondence to: Xiaofan Li - xli@sutrobio.com, Arturo Molina - amolina@sutrobio.com Keywords: CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001 About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 29, 2022, entitled, “Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.” Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo. To assess the chemotherapeutic potential of 15d-PMJ2, researchers Daniel A. Ladin, Margaret M. Nelson, Estefani Cota, Catherine Colonna, Colin Burns, Jacques Robidoux, Kelsey H. Fisher-Wellman, and Rukiyah Van Dross-Anderson from East Carolina University and University of North Carolina at Chapel Hill sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity. B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death. “Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death.” PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, the researchers showed that the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity. “The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.” DOI: https://doi.org/10.18632/oncotarget.28334 Correspondence to: Rukiyah Van Dross-Anderson - vandrossr@ecu.edu Keywords: calcium, mitochondrial respiration, endoplasmic reticulum stress, cancer, prostamide About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 29, 2022, entitled, “Impact of Covid-19 on the management of patients with metastatic melanoma.” The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated. In this study, researchers Michèle Welti, Phil F. Cheng, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer, and Laurence Imhof from University Hospital Zurich, University of Zurich and ETH Zurich analyzed all patients with metastatic melanoma receiving therapy at the Department of Dermatology at the University Hospital Zürich who developed Covid-19 between February 2020 and February 2022. “We retrospectively collected demographic data, cancer-specific parameters, melanoma treatment regimen, comorbidities and Covid-19-specific parameters in these patients.” Of the 350 patients with metastatic melanoma, 25 had Covid-19. The median age at the time of Covid-19 diagnosis was 66 years (range 36–86), 10 patients were female and 15 patients were male. The treatment regimen during infection was immunotherapy in 12 cases, followed by targeted therapy (n = 8), chemotherapy (n = 2) and TVEC injections, follow-up and palliative therapy in 1 case each. The severity was mild in 17 patients and 8 had a moderate to critical course. Patients with a severe Covid-19 course were often older and had more comorbidities than patients with a mild infection. Many of the patients had a mild Covid-19 course despite having metastatic melanoma and systemic therapy. “We therefore recommend continuing systemic therapy whenever possible, even in such exceptional situations as the Covid-19 pandemic.” DOI: https://doi.org/10.18632/oncotarget.28333 Correspondence to: Michèle Welti - michele.welti@uzh.ch Keywords: metastatic melanoma, Covid-19, Sars-CoV-2, immunotherapy, targeted therapy About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a trending research paper published by Oncotarget: "Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model." _________________________________________________________ The average age of patients with acute myeloid leukemia (AML) is 67 years old. Older adults generally have a lower tolerance for treatments that exhibit high off-target toxicity. Additionally, chemotherapy-relapsed or -refractory (R/R) AML patients are often at an advanced stage of disease and are therefore more likely to have comorbidities that may reduce their tolerance for harsh treatments. Thus, pharmaceutical AML drugs with high efficacy and low toxicity are in high demand. Antibody drug conjugates (ADCs) are emerging as promising therapeutic approaches to more safely treat hematological malignancies by reducing side effects. ADCs are designed to decrease damage to healthy tissues by specifically targeting tumor-associated antigens attached to cancer cells. “Antibody drug conjugates (ADC) are one of the modalities that aims to dissociate drug efficacy from toxicity. ADC consists of three components: antibody specific for tumor associated antigen, drug linker and cytotoxic payload.” ASTELLAS PHARMA Recently, researchers from Astellas Pharma Inc. (a pharmaceutical company in Japan) developed ASP1235—a novel ADC that targets Fms-like tyrosine kinase 3 (FLT3). In more than 90% of AML patients, FLT3 is overexpressed on leukemic blasts. ASP1235 is designed to target FLT3-positive leukemia cells and deliver the cytotoxic drug payload to these cells. However, this drug alone was found to have only a mild effect on AML cells, prompting researchers to assess the efficacy of ASP1235 in combination with other drugs. In a new study, Astellas Pharma researchers Hirofumi Tsuzuki, Tatsuya Kawase, Taisuke Nakazawa, Masamichi Mori, and Taku Yoshida investigated the efficacy of ASP1235 combined with venetoclax (an anti-apoptotic agent) and azacitidine (a DNA methyltransferase inhibitor) in an experimental mouse model of AML. Their research paper was published in Oncotarget on December 20, 2022, and entitled, “Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model.” Full blog: https://www.oncotarget.org/2023/01/04/novel-antibody-drug-conjugate-improves-murine-acute-myeloid-leukemia/ DOI: https://doi.org/10.18632/oncotarget.28331 Corresponding author: Hirofumi Tsuzuki - hirofumi.tsuzuki@astellas.com Keywords: acute myeloid leukemia (AML), ASP1235, antibody drug conjugate (ADC), venetoclax, azacitidine About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on December 20, 2022, entitled, “Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression.” One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune-tolerant microenvironment. In this new study, researchers Hongyan Yuan, Lu Jin, Handan Xiang, Anannya Bhattacharya, Philip E. Brandish, Gretchen Baltus, Alexander Tong, Changyan Zhou, and Robert I. Glazer from Georgetown University Medical Center, Merck Research Institute and Bicycle Therapeutics aimed to determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1). A conditional model of mammary fibrosis recently developed by this team, NeuT/ATTAC mice, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab. The researchers monitored drug response by tumor development, imaging mass cytometry, immunohistochemistry, and tumor gene expression by RNAseq. “Utilizing this more stringent tumor model to test its susceptibility to anti-PD-1 immunotherapy, we report the signaling processes associated with its lack of responsiveness.” Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1, and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors. “Overall, the immune tolerant TME in NeuT/ATTAC mice was associated with tumor-infiltrating macrophages, Foxp3+/PD-1- Treg cells as well as upregulation of the Wnt signaling pathway, which may provide further insights into the therapeutic options that may enhance immune checkpoint therapy.” DOI: https://doi.org/10.18632/oncotarget.28330 Correspondence to: Robert I. Glazer - glazerr@georgetown.edu Keywords: PD-1, NeuT, Wnt, macrophages, mammary tumorigenesis About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “The role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies.” Pyrethroids are extensively used insecticides by virtue of insecticidal activity potential in Asia, especially India, and in different nations worldwide to counter mosquitoes and insects for household or agricultural needs. The continuous widespread and uncontrolled use of pyrethroids and its derivatives have influenced multiple deleterious effects resulting in a potential risk factor causing damage to organ systems. Allethrin and prallethrin are extensively used, yet their influences on human primary cells are very limited or under-reported. The potential mechanisms by which allethrin and prallethrin modulates human primary cells, especially the molecular mechanisms or interconnectivity of autophagy-apoptosis, their clinical relevance in human subjects or patients are not well defined. In the current study, researchers Jyothi Puvula, Narendra Maddu, Nagajothi Gutam, Asha Parimal, and Raghavendra B. Pongali from Sri Krishnadevaraya University, Queen Mary's College, Manipal University, and National Institute of Biomedical Genomics furnished the evidence that both allethrin and prallethrin user samples significantly induced Ccl2 mRNA expression, increased amount of reactive oxygen intermediate, inhibited membrane bound enzymes and altered membrane fluidity. Pyrethroid derivative users had induced levels of lipid peroxidation and induced binding activities of transcription factors(tfs) like CEBP-β and NF-AT. Pyrethroid derivatives induced autophagy, elicited intracellular Ca2+ concentration, calcineurin and regulated proapoptotic genes, DAPK1, Bim. “Our current study presumably comprises the initial investigation of a very new mechanism of pyrethroid derivatives-moderated programmed cell death in various cell sets or types, like human primary cells where-in this is a late event, is documented.” Hence, the current research study might be significant in the various pyrethroid derivatives-allied hematological-related cancers and immunosuppressant or auto-immune disorders. In the foremost instance, the researchers present data stating that pyrethroid derivatives induces multiple cell signaling cascades, like CEBP-β, NF-AT, ERK and MAPK having a role in autophagy thereby; synchronously effectively impact on the apoptosis, therefore causing hematological tumors and toxic or immune related disorders. “Overall this current study might facilitate to formulate therapeutics or intervention targets that might serve to decrease the effect or impact of pyrethroids derivatives by targeting the signaling cascade that serves to minimize the modulation of autophagy mediated apoptosis.” DOI: https://doi.org/10.18632/oncotarget.28328 Correspondence to: Raghavendra B. Pongali - raghavbiot@gmail.com Keywords: allethrin, prallethrin, autophagy, apoptosis, Ccl2 About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients.” A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers. In the current study, researchers Tomofumi Miura, Shuichi Mitsunaga, Juntaro Matsuzaki, Satoko Takizawa, Ken Kato, Atsushi Ochiai, and Takahiro Ochiya from National Cancer Center Research Institute, National Cancer Center Hospital, Keio University, Toray Industries, Inc., and Tokyo Medical University investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas, and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East. “The aim of the present study was to develop predictive models using serum miRNAs for patients who [were] admitted to a PCU [palliative care unit] ≤6 months after starting anti-tumor treatment.” The team investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels. The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The researchers assert that the present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC. “The present study developed a predictive model using miRNA for patients admitted to a PCU ≤6 months after starting anti-tumor treatment. The present models might offer objective criteria for oncologists to facilitate the referral of patients to the EPC.” DOI: https://doi.org/10.18632/oncotarget.28327 Correspondence to: Shuichi Mitsunaga - smitsuna@east.ncc.go.jp Keywords: microRNA, early palliative care, integration, cancer, referral About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. In this new study, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, University of Pennsylvania, and Perelman School of Medicine investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev). “The present study was designed to investigate the association between GH levels and overall survivals (OS) and progression free survival (PFS) in HCC patients treated with current standard, atezolizumab plus bevacizumab.” The study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). The Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups. Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37–80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053). “Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.” DOI: https://doi.org/10.18632/oncotarget.28322 Correspondence to: Ahmed Omar Kaseb - akaseb@mdanderson.org Keywords: growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of an editorial perspective published in Volume 13, entitled, "The future of bioorthogonal-chemistry for targeting of exosomes in precision medicine." ____________________________________________________________ Extracellular vesicles are membrane-bound vehicles released by cells into the extracellular environment. There are three known types of extracellular vesicles: microvesicles, apoptotic bodies and exosomes. Discovered in 1983, exosomes can be defined as packets of bio-nanoparticles released by cells containing bioactive molecules such as proteins, lipids and nucleic acids. Exosomes can deliver their payload to other cells and are now also recognized for their role in cell-to-cell communication. This makes exosomes attractive targets for precision medicine tactics. However, targeting exosomes is challenging due to their nano-size and reactive contents. Bioorthogonal-chemistry may provide a new approach for targeting exosomes in precision medicine. “Bioorthogonal is the name of a chemical reaction that can occur inside of living cells without interfering the naïve biological process [1, 2].” Bioorthogonal-chemistry allows for the attachment of bioactive molecules to the surface of exosomes without disturbing the native environment. Developed in the early 2000s, this strategy could potentially be used to deliver therapeutic drugs or bioactive molecules directly to the target site with high precision. Bioorthogonal-chemistry is still at an early stage of development, but it holds promise in precision medicine for the treatment of cancer and other illnesses. By providing a way to target exosomes with bioactive molecules, bioorthogonal-chemistry could help to significantly improve the efficacy of medical treatments. It could also reduce the side effects of current treatments and increase safety for patients. “The concept of bioorthogonal chemistry has inspired a generation of biologists to think about RNA editing and bioengineering of exosomes [3, 4].” Full blog - https://www.oncotarget.org/2022/12/20/a-new-method-of-targeting-exosomes-in-precision-medicine/ DOI - https://doi.org/10.18632/oncotarget.28323 Correspondence to - Mujib Ullah - ullah@stanford.edu About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ For media inquiries, please contact: media@impactjournals.com
Dr. Kerri Winters-Stone and Dr. Jacob Raber from Oregon Health and Science University, Portland, OR, describe a recent research paper they co-authored that was published by Oncotarget in Volume 13, entitled, “Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.” DOI - https://doi.org/10.18632/oncotarget.28310 Correspondence to - Jacob Raber - raberj@ohsu.edu Video - https://www.youtube.com/watch?v=XQK7MK7qfWY Abstract Purpose/Objectives: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention. Materials and Methods: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments. Results: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not. Conclusions: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28310 Press release - https://www.oncotarget.com/news/pr/oncotarget-association-of-fall-rate-and-functional-status-by-apoe-genotype-in-cancer-survivors-after-exercise-intervention/ Keywords - apoE, breast cancer, exercise intervention, fall rate, functional status About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published in Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” __________________________________________________ Hepatocellular carcinoma (HCC) is a highly aggressive cancer of the liver with a very poor prognosis; many patients pass away within a year of diagnosis. Currently, there is no effective screening method for HCC and thus, 80% of patients are diagnosed at advanced stages. This makes treatment difficult and often unsuccessful. As a result, new treatments for HCC are constantly being explored. Atezolizumab and bevacizumab are two standard therapies used to treat unresectable, advanced HCC. However, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, and University of Pennsylvania Perelman School of Medicine noticed a significant gap in research on biomarkers of response in advanced HCC patients treated with atezolizumab plus bevacizumab. The team conducted a new study aimed at beginning to close this gap. On December 6, 2022, their research paper was published in Oncotarget's Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” “This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).” Full blog - https://www.oncotarget.org/2022/12/08/plasma-growth-hormone-in-hcc-a-biomarker-of-response-to-atezo-bev/ DOI - https://doi.org/10.18632/oncotarget.28322 Correspondence to - Ahmed Omar Kaseb - akaseb@mdanderson.org Video - https://www.youtube.com/watch?v=r2_6kjhwOfM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28322 Keywords - growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).” Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome and is rapidly becoming one of the major causes of hepatic cirrhosis and hepatocellular carcinoma (HCC), although some cases of HCC have developed in non-cirrhotic livers [1–8]. Although the percentage of patients with NAFLD who ultimately progress to fibrosis and later to HCC is relatively small, the number is significant because of the sheer number of patients who have NAFLD. Because there are no reliable biomarkers to predict the risk of HCC in patients with NAFLD, designing effective and cost-effective surveillance programs aimed at prevention and early detection of HCC is difficult, if not impossible. Therefore, there is an urgent need to identify such biomarkers and especially those that may appear at different stages of progression toward HCC. In the current study, researchers Mamoun Younes, Lin Zhang, Baharan Fekry, and Kristin Eckel-Mahan from George Washington University School of Medicine and Health Sciences and McGovern Medical School at the University of Texas Health Science Center (UTHealth) studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. “The aim of this study was to determine the relationships between p-STAT3, c-Myc and P2-HNF4α expression in biopsies from livers with NAFLD as potential biomarkers of HCC risk.” All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 expression was associated with hypertension (p = 0.037). All c-Myc positive biopsies were from patients with obesity, diabetes and hypertension. Only c-Myc expression was associated with advanced fibrosis; three (60%) of the c-Myc positive cases were associated with advanced fibrosis in contrast to 7 (10%) of the 44 c-Myc negative cases (p = 0.011). “Based on these results, we hypothesize with the following sequence of events with progression of NAFLD: P2-HNF4α expression is followed by expression of p-STAT3 which in turn is followed by the expression of c-Myc. Additional larger studies are needed to confirm these findings.” DOI: https://doi.org/10.18632/oncotarget.28324 Correspondence to: Mamoun Younes - myounes@mfa.gwu.edu Video: https://www.youtube.com/watch?v=LVR29K6P5I4 Keywords: hepatocyte nuclear factor four alpha, steatohepatitis, immunohistochemistry, hepatocellular carcinoma, isoform To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on November 22, 2022, entitled, “Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis.” Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. In the current study, researchers Yuji Morine, Tohru Utsunomiya, Hisami Yamanaka-Okumura, Yu Saito, Shinichiro Yamada, Tetsuya Ikemoto, Satoru Imura, Shohei Kinoshita, Akiyoshi Hirayama, Yasuhito Tanaka, and Mitsuo Shimada from Tokushima University Graduate School, Keio University and Kumamoto University used metabolomics to discover potential biomarkers of hepatocellular carcinoma (HCC). The team investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis–time-of-flight mass spectrometry. They also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. “In the present study, we sought to discover reliable metabolomic biomarkers for HCC diagnosis by elucidating metabolic alterations in primary HCC tumor tissue compared with non-tumor tissue, and additionally by investigating the serum metabolomic profiles before and after curative hepatectomy.” Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (EAA) (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. The results of this study revealed striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identified the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC. “In this study, the major findings were (i) the metabolomic profile of HCC tumors differs not only compared with matched non-tumor liver tissue but also with CRLM tissue, (ii) the serum metabolome of HCC patients is altered by hepatectomy, and (iii) the three EAAs leucine, valine, and tryptophan are candidate metabolomic biomarkers for hepatocarcinogenesis. Notably, however, we found that the metabolic profiles of HCC tumor tissues of differing etiologies (HBV/HCV infection) could not be distinguished, nor could the profiles of non-tumor liver tissue from any of the patient subgroups.” DOI: https://doi.org/10.18632/oncotarget.28306 Correspondence to: Yuji Morine - ymorine@tokushima-u.ac.jp Keywords: metabolomics, essential amino acid, hepatocellular carcinoma, diagnostic biomarker To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new review was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more.” Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. In this new review paper, researchers Masahiko Shibata, Kotaro Nanno, Daigo Yoshimori, Takahiro Nakajima, Makoto Takada, Takashi Yazawa, Kousaku Mimura, Norio Inoue, Takafumi Watanabe, Kazunoshin Tachibana, Satoshi Muto, Tomoyuki Momma, Yoshiyuki Suzuki, Koji Kono, Shungo Endo, and Seiichi Takenoshita from Fukushima Medical University, Aizu Chuo Hospital, Aizu Oncology Consortium, Nippon Medical School, and Bange Kousei General Hospital reviewed the perspective of MDSCs with emerging evidence. “Here, we review the following: the phenotypes and origins of MDSCs; the mechanisms of immunosuppression by MDSCs; MDSC functions in the TME; MDSCs in benign disorders and physiology; and consideration of MDSC manipulation in cancer treatment.” Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs. ICI therapies have been developed and demonstrated surprising outcomes in many types of cancer. However, the effects of ICIs are not universal or uniformal in all cancer patients, and emerging evidence has indicated that MDSCs are a crucial target to overcome this important issue with a growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are under exploration, some of which have been used in clinical trials. “More studies are required for the development of more effective strategies against MDSCs.” DOI: https://doi.org/10.18632/oncotarget.28303 Correspondence to: Masahiko Shibata - mshibata@fmu.ac.jp Video: https://youtu.be/ZJj6CzcJ6x4 Keywords: MDSC, immunosuppression, Treg, TAM, cancer About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.” Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. In this new study, researchers Gwendolyn J. McGinnis, Sarah Holden, Betty Yu, Charlton Ransom, Carolyn Guidarelli, Brian De, K Diao, David Boyce, Charles R. Thomas Jr., Kerri Winters-Stone, and Jacob Raber from the University of Texas MD Anderson Cancer Center, Oregon Health and Science University and Dartmouth-Hitchcock's Dartmouth Cancer Center tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention. “In the current analyses, the modulating effect of apoE genotype on functional status and symptom burden in response to exercise intervention was investigated in a subsample of trial participants.” Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments. Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not. “The study findings suggest that APOE genotype may be associated with presence and severity of cancer treatment-related side effects and symptoms and also influence the response to exercise-based interventions in cancer survivors.” DOI: https://doi.org/10.18632/oncotarget.28310 Correspondence to: Jacob Raber - raberj@ohsu.edu Video: https://www.youtube.com/watch?v=CvN9ZDWymz8 Keywords: apoE, breast cancer, exercise intervention, fall rate, functional status About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new research perspective was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Treasures from trash in cancer research.” Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets. In this new research perspective, researchers Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção from Instituto Metrópole Digital at the Universidade Federal do Rio Grande do Norte and Núcleo de Pesquisas em Oncologia and Instituto de Ciências Biológicas at the Universidade Federal do Pará used metagenomic tools to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated. “Here, we demonstrate potential strategies to benefit from nontargeted information resulting from high-throughput cancer investigations.” In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found. These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run. “Altogether, our results strengthen the hypothesis that abundant additional and potentially useful information can be extracted from NGS. Moreover, the integrated investigation of every available information should provide a broader and more robust interpretation of the molecular scenario from each experiment.” DOI: https://doi.org/10.18632/oncotarget.28308 Correspondence to: Paulo Pimentel de Assumpção - assumpcaopp@gmail.com Video: https://www.youtube.com/watch?v=etqlRWCdhI0 Keywords: cancer metagenomics, cancer sncRNA expression, RNA-Seq variant calling About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas.” Comprehensive genomic analyses of tumor biopsies from patients with newly-diagnosed germinal center B cell (GCB) diffuse large B cell/high grade B cell lymphoma (DLBCL/HGBL) have identified molecular subtypes predictive of inferior survival, which are characterized by somatic mutations that can be detected through clinical laboratory mutation analysis (CLMA). To determine the frequency and predictive value of individual genetic mutations associated with these experimentally-defined poor-risk subgroups, researchers Daniel J. Landsburg, Jennifer J.D. Morrissette, Stephen J. Schuster, Sunita D. Nasta, James N. Gerson, Stefan K. Barta, Jakub Svoboda, Elise A. Chong, and Megan S. Lim from the University of Pennsylvania reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at the University of Pennsylvania. “Thus, we sought to analyze the results of CLMA performed at our institution on tumors from patients with newly-diagnosed GCB DLBCL/HGBL previously-treated with first line immunochemotherapy to determine the frequency and predictive value of the presence of individual genetic mutations associated with these experimentally-defined poor-risk subgroups.” CLMA was successfully performed on 58/59 patient tumor biopsies with a median turnaround time of 16 days, and 51 on which CLMA was routinely performed with adequate clinical follow-up were analyzed. Patients whose tumors demonstrated CREBBP mutation experienced a lower estimated rate of 2-year disease free survival (DFS) as compared to those whose tumors did not (45% [95% CI 18–68%] vs. 67% [95% CI 44–83%], P = 0.045). The researchers note that CREBBP mutations may be frequent and predict for inferior DFS in patients with newly-diagnosed GCB DLBCL/HGBL. Furthermore, CLMA may be practically-applied to translate experimental findings into those with more direct application to risk stratification and clinical trial design in subsets of patients with DLBCL/HGBL. “In conclusion, CLMA performed on tumor biopsies from patients with newly-diagnosed GCB DLBCL/HGBL revealed frequent mutations in CREBBP which were predicted to result in loss of function as well as a significantly lower rate of estimated DFS at 2 years.” DOI: https://doi.org/10.18632/oncotarget.28309 Correspondence to: Daniel J. Landsburg Email: daniel.landsburg@pennmedicine.upenn.edu Video: https://www.youtube.com/watch?v=yqTQOv8Vufc Keywords: diffuse large B cell lymphoma, high grade B cell lymphoma, mutation analysis, next generation sequencing, chemotherapy About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a research paper published in Volume 13, entitled, "Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer." _______________________________________________ Neoadjuvant chemotherapy (NAC) is a type of cancer treatment involving the administration of chemotherapy drugs before surgery. The goal of NAC is to shrink the tumor(s) in order to make it/them easier to remove during surgery and to decrease the chance of cancer recurrence after treatment. NAC is typically well tolerated by patients and has been shown to improve outcomes in patients with bladder cancer. Predictive biomarkers are being increasingly used in oncology to identify patients who are likely to respond to chemotherapy. In the past, the decision to administer chemotherapy was based on tumor type and stage. However, it is now understood that there is considerable heterogeneity within these groups, and that not all patients will respond to the same treatment. Predictive biomarkers can help to overcome this challenge by identifying those patients who are most likely to benefit from chemotherapy. There are a number of different types of predictive biomarkers, which can be divided into two broad categories: tumor biomarkers and host biomarkers. Tumor biomarkers are usually specific to the tumor type and can include markers of cell proliferation and DNA repair. Host biomarkers are usually found in the blood or other bodily fluids and can include markers of inflammation, immune function and metabolism. The use of predictive biomarkers has the potential to improve the efficacy of chemotherapy and reduce toxicity by avoiding its use in patients who are unlikely to benefit. In a new study, researchers Neal Murphy, Andrew J. Shih, Paras Shah, Oksana Yaskiv, Houman Khalili, Anthony Liew, Annette T. Lee, and Xin-Hua Zhu from Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health Cancer Institute, Feinstein Institutes for Medical Research, and Mayo Clinic aimed to develop and validate a predictive biomarker panel for response to NAC in patients with muscle-invasive bladder cancer (MIBC). Their research paper was published on November 2, 2022, in Oncotarget's Volume 13, entitled, “Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.” Full blog - https://www.oncotarget.org/2022/11/15/biomarkers-may-predict-neoadjuvant-chemosensitivity-in-bladder-cancer/ DOI - https://doi.org/10.18632/oncotarget.28302 Correspondence to - Neal Murphy - nmurphy2@northwell.edu, Annette T. Lee - alee@northwell.edu, and Xin-Hua Zhu - xzhu1@northwell.edu Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-predictive-molecular-biomarkers-for-determining-neoadjuvant-chemosensitivity-in-muscle-invasive-bladder-cancer Keywords - muscle invasive bladder cancer, neoadjuvant chemotherapy, gene expression, molecular subtyping, canonical correlation analysis About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
A new research paper was published in Oncotarget's Volume 13 on November 2, 2022, entitled, “MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.” Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. In this new study, researchers Jen-Chieh Lee, Shu Liu, Yucheng Wang, You Liang, and David M. Jablons from the University of California San Francisco and Touro University sought to examine the anticancer effect of MK256 on AML. “In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation.” Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. “Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.” DOI: https://doi.org/10.18632/oncotarget.28305 Correspondence to: Jen-Chieh Lee -jenchieh.lee@ucsf.edu, Shu Liu - shu.liu@ucsf.edu Keywords: AML, CDK8, kinase inhibitor, STAT pathway, xenograft Video: https://www.youtube.com/watch?v=8bRgqTg9-c8 About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on October 20, 2022, entitled, “Nectin-4 is widely expressed in head and neck squamous cell carcinoma.” Nectin-4 has been successfully established as a target molecule in locally advanced and metastatic bladder cancer. An antibody-drug conjugate (enfortumab-vedotin) directed against nectin-4 has shown marked tumor remission rates in this tumor type, which is known for high expression rates of nectin-4. As head and neck cancer and urothelial carcinomas share morphological and molecular similarities, researchers Christine Sanders, Jan-Frederic Lau, Dimo Dietrich, Sebastian Strieth, Peter Brossart, and Glen Kristiansen from University Medical Center Bonn and University Hospital Bonn aimed to evaluate Nectin-4 expression in head and neck squamous cell carcinoma (HNSCC). A previously described and clinically characterized cohort of HNSCC (n = 159) was analyzed by immunohistochemistry for Nectin-4 expression. The expression data was correlated to clinico-pathological parameters including patient outcome. Nectin-4 was found in 86.2% of HNSCC, with medium/high expression seen in 32.7% of cases. Non smokers and p16 positive HNSCC showed a higher expression of Nectin-4 (p < 0.005). There was no correlation of Nectin-4 with grading or tumor stage. Nectin-4 positive tumors showed significantly better survival (log rank p = 0.006). “Similar to urothelial carcinoma, Nectin-4 is found in the majority of HNSCC, which clearly warrants further studies to clarify if HNSCC also respond to targeted therapy with enfortumab-vedotin. Moreover, expression of Nectin-4 is associated with HPV infection and may serve as a prognostic marker in HNSCC.” DOI: https://doi.org/10.18632/oncotarget.28299 Correspondence to: Glen Kristiansen - Email: glen.kristiansen@ukbonn.de Video - https://www.youtube.com/watch?v=tDY21YpFsKc Keywords: Nectin-4, enfortumab-vedotin, HNSCC, p16 About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
Listen to a blog summary about a research perspective published in Volume 13 of Oncotarget, entiutled, "FSP1, a novel KEAP1/NRF2 target gene regulating ferroptosis and radioresistance in lung cancers." __________________________________________________ Ferroptosis is a type of cell death caused by the accumulation of iron and lipid peroxides in cells. Cancer cells are often resistant to ferroptosis, which allows them to survive and proliferate. Radioresistance is another common feature of cancer cells that allows them to resist the effects of radiation therapy. A new research paper (published on April 22, 2022) identified ferroptosis suppressor protein 1 (FSP1) as a novel KEAP1/NRF2 target gene and demonstrated that FSP1 plays an essential role in NRF2-mediated ferroptosis resistance and radioresistance in KEAP1-deficient lung cancer cells. Recently, researchers Nsengiyumva Emmanuel, Hongen Li, Jing Chen, and Yilei Zhang from Xi'an Jiaotong University, Ruyang People's Hospital and Shaanxi Jiuzhou Biomedical Science and Technology Group wrote a paper about the implications of these findings. On October 19, 2022, their research perspective was published in Oncotarget's Volume 13, entitled, “FSP1, a novel KEAP1/NRF2 target gene regulating ferroptosis and radioresistance in lung cancers.” “In a recent study by Pranavi Koppula et al. from The University of Texas MD Anderson Cancer Center, FSP1 was demonstrated as a novel target of NRF2 and to play a vital role in KEAP1/NRF2-mediated ferroptosis regulation [13], which reveals the important role of genetic regulation of FSP1 in cancer development.” Full blog - https://www.oncotarget.org/2022/11/02/new-target-fights-ferroptosis-and-radio-resistance-in-lung-cancers/ DOI - https://doi.org/10.18632/oncotarget.28301 Correspondence to - Yilei Zhang - zhangyilei@xjtu.edu.cn Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28301 Keywords - KEAP1/NRF2, lung cancer, ferroptosis, radioresistance, therapy About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- October 27, 2022 – On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by MEDLINE/PubMed and PubMed Central/PubMed. *** The United States government is firmly committed to making credible biomedical research available to the public. In operation since 1996, PubMed is an online biomedical literature database operated by the U.S. National Institutes of Health (NIH). PubMed provides free access to over 34 million citations from MEDLINE, PubMed Central (PMC) and the National Center for Biotechnology Information databases. Started back in the 1960s, MEDLINE is a large bibliographic citation and abstract database for life science articles in journals and other scientific publications. MEDLINE now contains more than 29 million references to articles in over 5,200 journals. In 2000, PMC was launched as a free, full-text archive of biomedical and life sciences journal literature. Both MEDLINE and PMC are operated by the NIH's National Library of Medicine. Importantly, PubMed and MEDLINE use the same controlled vocabulary thesaurus, called Medical Subject Headings, or MeSH, to ensure that content is easily searchable and properly indexed. The vast scope of scholarly publications in MEDLINE is why Oncotarget is proud to have its papers indexed by this database. Oncotarget, launched in 2010, is a peer-reviewed, open-access and primarily oncology-focused biomedical journal. This journal has international reach—publishing research from world-renowned institutions. The cornerstones of Oncotarget's publishing practices are insightful peer review, scientific integrity, rigorous ethical standards, up-to-date tools and resources, and a commitment to local and scientific communities. Oncotarget aims to maximize research impact, eliminate borders between specialties and foster the application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.” The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized, highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). “The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration.” In a new study, researchers Diala Ghazal, Fatma Zalzala, John C. Fisk, Swetha Tati, Loukia G. Karacosta, Susan Morey, James R. Olson, Sally Quataert, Grace K. Dy, and Kate Rittenhouse-Olson from For-Robin, Inc, University at Buffalo, University of Rochester, and Roswell Park Comprehensive Cancer Center Buffalo aimed to assess the potential therapeutic efficacy of these antibodies by treating four human cancer- mouse xenograft models with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice. H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site. “In conclusion, both H2aL2a and H3L3 humanized antibodies to TF-Ag-α show efficacy in in vivo xenograft models of human tumors in SCID and nude mice and thus hold promise as therapeutics for breast and lung cancer. H2aL2a significantly decreased tumor growth rate in both breast cancer and both lung cancer models tested. H2aL2a is equal to or better than H3L3 in four of the four models and H2aL2a cell lines have far superior antibody production capabilities under the conditions tested.” DOI: https://doi.org/10.18632/oncotarget.28282 Correspondence to: Kate Rittenhouse-Olson - krolson@buffalo.edu Keywords: hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com. Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.” Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. Previously, researchers Romana Moench, Martin Gasser, Karol Nawalaniec, Tanja Grimmig, Amrendra K. Ajay, Larissa Camila Ribeiro de Souza, Minghua Cao, Yueming Luo, Petra Hoegger, Carmen M. Ribas, Jurandir M. Ribas-Filho, Osvaldo Malafaia, Reinhard Lissner, Li-Li Hsiao, and Ana Maria Waaga-Gasser, from Harvard Medical School, Shenzhen Traditional Chinese Medicine Hospital, University of Wuerzburg, and Mackenzie Evangelical Faculty of Paraná, recently provided evidence for upregulation of PDGF expression in UICC stage I–IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. In their new study, the researchers sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC. “Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRβ, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors.” Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. The team then analyzed several CRC cell lines for PDGFRα, PDGFRβ, VEGFR1, and VEGFR2 protein expression. They found these receptors to be variably expressed amongst the investigated cell lines. Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor. “Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.” DOI: https://doi.org/10.18632/oncotarget.28281 Correspondence to: Ana Maria Waaga-Gasser - awaaga@bwh.harvard.edu Keywords: PDGF, VEGFR, EGFR, bypassed signaling, colorectal cancer About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com. Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
Listen to a blog summary of a recently published research paper in Volume 13 of Oncotarget, entitled, "HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs." _______________________________________ Chromatin constitutes chromosomes in eukaryotic cells and comprises DNA and proteins. Chromosomes produce proteins and enzymes that are essential for cellular function and maintenance, including DNA repair. A critical process for DNA repair is poly(ADP-ribosyl)ation, or PARylation. PARylation is triggered by poly(ADP ribose) polymerase (PARP) enzymes. When DNA becomes damaged, PARP enzymes bind to the damaged location in the cell. In cancer cells, however, this natural process can be counterproductive in respect to cancer treatment. PARylation can produce DNA repair mechanisms in cancer cells that can lead to the evasion of cell death, and even drug resistance. Inhibiting PARylation may be a viable therapeutic strategy for cancer treatment. Histones, the main proteins that constitute chromatin, undergo post-translational modifications that regulate gene expression. Histone acetylation is an important epigenetic process that affects gene expression by relaxing the chromatin structure, making chromatin remodeling more feasible. Histone deacetylases (HDACs) are enzymes that can have the opposite effect. Histone deacetylation makes the chromatin more compact and difficult to remodel. The overexpression of HDAC has also been associated with tumorigenesis. Histone deacetylase inhibitors (HDACi) are a class of therapeutics that have shown promise in the treatment of hematologic malignancies (blood cancer) and solid tumors. In a new study, researchers Benigno C. Valdez, Yago Nieto, Bin Yuan, David Murray, and Borje S. Andersson from the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center and the Cross Cancer Institute's Department of Experimental Oncology at the University of Alberta investigate the efficacy of HDACi in combination with PARP inhibitors (PARPi) and chemotherapeutic drugs to treat hematologic cancer. On October 14, 2022, their research paper was published in Volume 13 of Oncotarget, entitled, “HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs.” Full blog - https://www.oncotarget.org/2022/10/19/synergy-of-hdaci-parpi-and-chemotherapeutics-against-blood-cancer/ DOI - https://doi.org/10.18632/oncotarget.28278 Correspondence to - Benigno C. Valdez - bvaldez@mdanderson.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28278 Keywords - poly(ADP-ribosyl)ation, HDAC inhibitors, PARP inhibitors, chemotherapy, hematologic malignancy About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on October 8, 2022, entitled, “Effectiveness of radiotherapy for local control in T3N0 rectal cancer managed with total mesorectal excision: a meta-analysis.” The total mesorectal excision (TME) significantly improves rectal cancer outcomes. Radiotherapy's benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated. In a new study, researchers Michael Jonathan Kucharczyk, Andrew Bang, Michael C. Tjong, Stefania Papatheodoru, and Jesus C. Fabregas from Nova Scotia Cancer Centre, Dalhousie University, BC Cancer – Vancouver, Princess Margaret Cancer Centre, Harvard T.H. Chan School of Public Health, and University of Florida Health Cancer Center conducted a systematic review and meta-analysis to determine whether radiotherapy alteres the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME. “This systematic review identified unique 7 retrospective cohort studies which evaluated whether radiotherapy reduces LR in T3N0 rectal cancer patients managed with TME.” The studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty. All were performed independently by at least two investigators. Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted. Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4–78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy. A non-significant LR benefit with radiotherapy's addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted. “With low certainty, this meta-analysis observed a non-significant benefit with radiotherapy to 5-year LR rates among T3N0 rectal cancer patients that received a TME. Until a pragmatically sized randomized control trial is completed, our research adds a layer of data to facilitate informed and personalized treatment decisions for T3N0 rectal cancer patients, albeit with potential significant bias from solely relying on retrospective cohort studies.” DOI: https://doi.org/10.18632/oncotarget.28280 Correspondence to: Michael Jonathan Kucharczyk - michael.kucharczyk@medportal.ca Keywords: radiotherapy, meta-analysis, systematic review, rectal cancer, total mesorectal excision About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on October 8, 2022, entitled, “In vitro chemotherapy-associated muscle toxicity is attenuated with nutritional support, while treatment efficacy is retained.” Muscle-wasting and treatment-related toxicities negatively impact prognosis of colorectal cancer (CRC) patients. Specific nutritional composition might support skeletal muscle and enhance treatment support. In this new in vitro study, researchers Liza A. Wijler, Francina J. Dijk, Hanil Quirindongo, Danielle A.E. Raats, Bram Dorresteijn, Matthew J.W. Furber, Anne M. May, Onno Kranenburg, and Miriam van Dijk, from University Medical Centre Utrecht, Danone Nutricia Research and Utrecht University, assessed the effect of nutrients eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), L-leucine, and vitamin D3 as single nutrients or in combination on chemotherapy-treated C2C12-myotubes and specific CRC-tumor cells. Using C2C12-myotubes, the effects of chemotherapy (oxaliplatin, 5-fluorouracil, oxaliplatin+5-fluorouracil and irinotecan) on protein synthesis, cell-viability, caspase-3/7-activity and lactic acid dehydrogenase (LDH)-activity were assessed. Addition of EPA, DHA, L-leucine and vitamin D3 and their combination (SNCi) were studied in presence of above chemotherapies. Tumor cell-viability was assessed in oxaliplatin-treated C26 and MC38 CRC cells, and in murine and patient-derived CRC-organoids. While chemotherapy treatment of C2C12-myotubes decreased protein synthesis, cell-viability and increased caspase-3/7 and LDH-activity, SNCi showed improved protein synthesis and cell viability and lowered LDH activity. The nutrient combination SNCi showed a better overall performance compared to the single nutrients. Treatment response of tumor models was not significantly affected by addition of nutrients. “This in vitro study shows protective effect with specific nutrition composition of C2C12-myotubes against chemotherapy toxicity, which is superior to the single nutrients, while treatment response of tumor cells remained.” DOI: https://doi.org/10.18632/oncotarget.28279 Correspondence to: Miriam van Dijk – Email: miriam.vandijk@danone.com Keywords: C2C12 myotubes, chemotherapy, chemotherapy-associated toxicity, colorectal cancer, nutrients, tumor (organoid) cells About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
Blog summary of a trending research paper published by Oncotarget, entitled, "Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival." _________________________________________ Genetic interactions involved in the survival of cancer cells are potential therapeutic targets in personalized cancer therapy. “Synthetic lethal” is a type of genetic interaction where the knockout of one gene can cause cell death but only in the presence of another dependent gene. Cancer researchers view synthetic lethality screening as a powerful tool in precision medicine. “Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology.” Poly-ADP-ribose polymerase 10, or PARP10, is a nuclear protein that is overexpressed in multiple cancers. Genetic susceptibilities based on PARP10 expression levels in an individual may be potential targets for personalized cancer therapy. In a new study, researchers Jude B. Khatib, Emily M. Schleicher, Lindsey M. Jackson, Ashna Dhoonmoon, George-Lucian Moldovan, and Claudia M. Nicolae, from the Department of Biochemistry and Molecular Biology at Penn State College of Medicine, used CRISPR-based, genome-wide genetic screens to identify potential synthetic lethality interactions with PARP10-overexpressing and -knockout cancer cells. On September 28, 2022, their research paper was published in Oncotarget and entitled, “Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival.” “Here, we employed complementary CRISPR loss-of-function genome-wide screening to identify genes required for proliferation of PARP10-overexpressing and PARP10-knockout cells.” Full blog - https://www.oncotarget.org/2022/10/07/crispr-screens-identify-novel-targets-for-personalized-cancer-therapy/ DOI - https://doi.org/10.18632/oncotarget.28277 Correspondence to - Claudia M. Nicolae - cmn14@psu.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28277 Keywords - PARP10, ATM, CRISPR screens, genome stability, cancer cell proliferation About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on September 28, 2022, entitled, “Genomic alterations predictive of poor clinical outcomes in pan-cancer.” Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts. In this new study, researchers Crystal S. Seldon, Karthik Meiyappan, Hannah Hoffman, Jimmy A. Guo, Neha Goel, William L. Hwang, Paul L. Nguyen, Brandon A. Mahal, and Mohammed Alshalalfa from the University of Miami, Massachusetts General Hospital, Broad Institute of MIT, University of California San Francisco, and Dana-Farber Cancer Institute and Brigham and Women's Hospital used pan-cancer cohorts from The Cancer Genome Atlas (TCGA) and the MSK-IMPACT study to evaluate the associations of common genomic alterations with poor clinical outcome. “There is growing interest in genomic profiling (i.e. tumor mutations, copy number (CN) alterations) for cancer therapy and precision oncology to inform treatment decisions and identify patients for relevant clinical trials [1].” Full press release - https://www.oncotarget.net/2022/10/04/oncotarget-genomic-alterations-predictive-of-poor-clinical-outcomes-in-pan-cancer/ DOI: https://doi.org/10.18632/oncotarget.28276 Correspondence to: Mohammed Alshalalfa - mohamed.alshalalfa@gmail.com Keywords: genomic alterations, TP53, TCGA, poor prognosis About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on September 14, 2022, entitled, “Site of analysis matters – Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation.” Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease, which cannot be treated with chemoradiotherapy or salvage surgery, systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy, programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging, including in patients with anal cancer. “Altogether, there is little data on PD-1 treatment in HIV infected patients.” In a new study, researchers Melanie Demes, Ursula Pession, Jan Jeroch, Falko Schulze, Katrin Eichler, Daniel Martin, Peter Wild, and Oliver Waidmann from Universitätsklinikum Frankfurt and Centrum für Hämatologie und Onkologie reported a case of an HIV infected patient with anal cancer, microsatellite instability (MSI) high status, a high mutation frequency regarding tumor mutational burden (TMB) and an ongoing response to Nivolumab. “We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment.” Thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. The researchers concluded that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor. “According to our results, we propose to assess mutational status in tissue from metastasis rather than from the primary site when additional molecular analyses are performed for treatment decisions.” DOI: https://doi.org/10.18632/oncotarget.28274 Correspondence to: Oliver Waidmann – Emails: oliver.waidmann@kgu.de Keywords: anal cancer, microsatellite instability, immunotherapy, high-throughput nucleotide sequencing, nivolumab About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Blog summary of a research paper recently published by Oncotarget, entitled, "Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma." _____________________________________ Altitude is considered any elevation above sea level. Higher altitude environments are known to influence various physiological processes in the human body, including those related to hypoxia-inducing factors (HIF), vitamin D, ultraviolet radiation, oxygen toxicity, and changes in pH. Researchers have suggested that altitude may even affect the development and progression of some diseases, including stomach/gastric cancer. “Gastric cancer is the third leading cause of death in the world and is estimated to cause almost 15 million deaths by 2035 [2].” Gastric Cancer & Altitude The primary subtype of gastric cancer is gastric adenocarcinoma (GA). GA develops in the mucus-secreting cells that line the stomach (gastric epithelium). Higher incidence rates of GA have been found among populations living at high altitudes. High altitudes are notorious for low air pressure and decreased oxygen saturation levels. Decreases in oxygen (hypoxia) can activate the transcriptional regulator hypoxia-inducing factor-1 (HIF-1). HIF-1 is known to be upregulated in a variety of human cancers, including GA. The role of HIF-1 in GA pathogenesis and prognosis has not yet been fully understood. “Gastric adenocarcinoma (GA) has a high incidence in Ecuador, in men it ranks third and in women it ranks fifth.” There is a higher incidence of GA among people living in Ecuador. This is a country that straddles the equator yet, the altitude in Ecuador varies significantly across the country. For example, the altitude is 2,850 meters in the capital city of Quito (the second-highest capital city in the world). In Guayaquil (a coastal city in Ecuador) the altitude is only nine meters. These facts make Ecuador an optimal location for studying the effects of altitude on gastric adenocarcinoma. “Ecuador has a varied altitude diversity and there is a differential incidence of cancer between populations living in the Andean or mountainous region when compared to coastal populations or living at low altitude.” Full blog - https://www.oncotarget.org/2022/09/27/how-high-altitudes-influence-hif-1-gastric-cancer-patient-survival/ DOI - https://doi.org/10.18632/oncotarget.28275 Correspondence to - José Sebastiao dos Santos - lab.biomol.cirugia@fmrp.usp.br Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28275 Keywords - cancer, gastric adenocarcinoma, hypoxia-induced factor, HER2, survival rate, tumor markers About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published by Oncotarget, entitled, "Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model." _________________________________________ Esophageal cancer is the sixth most common cause of death from cancer worldwide. The two main types of esophageal cancer are adenocarcinoma and esophageal squamous cell carcinoma (ESCC). ESCC arises from the cells lining the esophagus, and it is most common in areas of the world where tobacco use and alcohol consumption are high. “Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment.” Researchers Raghibul Hasan, Gunjan Srivastava, Akram Alyass, Rinu Sharma, Anoop Saraya, Tushar K. Chattopadhyay, Siddartha DattaGupta, Paul G. Walfish, Shyam S. Chauhan, and Ranju Ralhan from All India Institute of Medical Sciences, Mount Sinai Hospital Toronto, McMaster University, Guru Gobind Singh Indraprastha University, and the University of Toronto conducted a new study on the protein expression-based risk model they developed to predict recurrence-free survival for ESCC patients. On September 14, 2022, their research paper was published in Oncotarget's Volume 13, and entitled, “Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model.” “Our study is important because: (i) it is based on changes in expression levels of the biomarker proteins in different subcellular compartments and is not limited to alterations in the overall protein expression levels; (ii) investigates the comprehensive clinical relevance of subcellular alterations in expression of multiple key components of Wnt pathway in the same ESCC patients' cohort; (iii) correlates these findings with disease outcome and (iv) develops a Biomarker risk score for defining the risk of recurrence of ESCCs.” Full blog - https://www.oncotarget.org/2022/09/23/protein-based-risk-model-predicts-esophageal-cancer-recurrence/ DOI - https://doi.org/10.18632/oncotarget.10656 Correspondence to - Ranju Ralhan - rralhan@mtsinai.on.ca, Shyam S. Chauhan - s_s_chauhan@hotmail.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.10656 Keywords - esophageal cancer, wnt proteins, disheveled, molecular markers, prognosis About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- September 20, 2022 – A new research paper was published in Oncotarget's Volume 13 on September 14, 2022, entitled, “Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy.” Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively, and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. Researchers Daiki Ueno, Juan C. Vasquez, Amrita Sule, Jiayu Liang, Jinny van Doorn, Ranjini Sundaram, Sam Friedman, Randy Caliliw, Shinji Ohtake, Xun Bao, Jing Li, Huihui Ye, Karla Boyd, Rong Rong Huang, Jack Dodson, Paul Boutros, Ranjit S. Bindra, and Brian Shuch from Yale University School of Medicine, West China Hospital/School of Medicine, Wayne State University, and University of California, Los Angeles have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs). “In this study, we sought to examine the activity of combined TMZ and PARPi in Krebs-cycle-deficient renal cancer models. Fh1 and Sdhb are the murine counter part of human FH and SDHB, respectively.” The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity. These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy. “Using newly developed Fh1 and Sdhb deficient syngeneic mouse models, we demonstrate that oncometabolite-induced HR defects can be leveraged with PARPi treatment to enhance sensitivity to low-dose TMZ in Krebs-cycle-deficient renal cancer.” DOI: https://doi.org/10.18632/oncotarget.28273 Correspondence to: Ranjit S. Bindra & Brian Shuch – Emails: Ranjit.Bindra@yale.edu & bshuch@mednet.ucla.edu Keywords: FH, SDHB, renal cell carcinoma, PARP inhibitor, temozolomide About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Dr. Balraj Singh from the Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, describes a recent research paper he co-authored that was published by Oncotarget, entitled, “Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine.” DOI - https://doi.org/10.18632/oncotarget.27922 Correspondence to - Anthony Lucci - alucci@mdanderson.org, and Balraj Singh - bsingh@mdanderson.org Video version - https://www.youtube.com/watch?v=TwIBNkUe1y4 Abstract Highly adaptable breast cancer cells that can opportunistically switch between proliferation and quiescence are often responsible for disease relapse. We have developed a function-based selection strategy for such resistant cells, exemplified by SUM149-MA and FC-IBC02-MA triple-negative breast cancer cells. We have also reported that a lengthy treatment with low-dose 6-mercaptopurine, a clinically useful anti-inflammatory drug, inhibits such resistant cells. To more rigorously test the clinical suitability of 6-mercaptopurine, here we investigated effects of further lowering its dose and the possibility of overcoming resistance to single-drug treatment by combining the drug with another ribonucleoside analog 5-azacitidine. We found that that a lengthy treatment with 1 μM 5-azacitidine, without a significant effect on cell proliferation, sensitized cancer cells to the inhibitory effects of low-dose 6-mercaptopurine. Importantly, treatment for several weeks with low doses of 6-mercaptopurine and/or 5-azacitidine did not render cancer cells resistant to chemotherapeutic drugs doxorubicin or paclitaxel. In fact, the cells became more sensitive to chemotherapeutic drugs upon treatment with 6-mercaptopurine and/or 5-azacitidine. Our analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in our model. Our results showed that safe drugs such as low-dose 6-mercaptopurine singly or combined with 5-azacitidine, which are suitable for use prior to disease relapse, have a potential of inhibiting highly resistant triple-negative breast cancer cells. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27922 Press release - https://www.oncotarget.com/news/pr/inhibition-of-resistant-triple-negative-breast-cancer-cells/ Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget on September 8, 2022, by researchers Jingwen Zhu, Joseph N. Miller and John D. Schuetz from St. Jude Children's Research Hospital in Memphis, Tennessee, entitled, “An ABC transporter as a potential target against SHH-Medulloblastoma: From Benchtop to Bedside.” Medulloblastoma (MB) is a common malignant pediatric brain tumor divided into four main subgroups (WNT, SHH, Group 3 and 4). The most prevalent MB in children
Dr. Glenn Simmons Jr. from Cornell University College of Veterinary Medicine, and Dr. Stefani Thomas from University of Minnesota School of Medicine, detail a recent review they co-authored that was published by Oncotarget, entitled, “Targeting lipid metabolism in the treatment of ovarian cancer.” DOI - https://doi.org/10.18632/oncotarget.28241 Correspondence to - Glenn E. Simmons Jr. - glenn.simmons@cornell.edu Abstract Cancer cells undergo alterations in lipid metabolism to support their high energy needs, tumorigenesis and evade an anti-tumor immune response. Alterations in fatty acid production are controlled by multiple enzymes, chiefly Acetyl CoA Carboxylase, ATP-Citrate Lyase, Fatty Acid Synthase, and Stearoyl CoA Desaturase 1. Ovarian cancer (OC) is a common gynecological malignancy with a high rate of aggressive carcinoma progression and drug resistance. The accumulation of unsaturated fatty acids in ovarian cancer supports cell growth, increased cancer cell migration, and worse patient outcomes. Ovarian cancer cells also expand their lipid stores via increased uptake of lipids using fatty acid translocases, fatty acid-binding proteins, and low-density lipoprotein receptors. Furthermore, increased lipogenesis and lipid uptake promote chemotherapy resistance and dampen the adaptive immune response needed to eliminate tumors. In this review, we discuss the role of lipid synthesis and metabolism in driving tumorigenesis and drug resistance in ovarian cancer conferring poor prognosis and outcomes in patients. We also cover some aspects of how lipids fuel ovarian cancer stem cells, and how these metabolic alterations in intracellular lipid content could potentially serve as biomarkers of ovarian cancer. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28241 Keywords - ovarian cancer, lipid metabolism, biomarkers, microenvironment, fatty acid About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a press release about a new research paper published by Oncotarget, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.” _______________________________ A new research paper was published in Oncotarget on September 6, 2022, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.” Bladder cancer (BC) is the 10th most common malignancy, affecting more than half a million people worldwide each year, and accounts for 4.6% of the total new cancer cases in the United States. With urothelial carcinoma (UC), the most common form of BC, the 5-year BC recurrence rate is nearly 78%, necessitating life-long surveillance, making it one of the costliest cancers to treat and manage. Cystoscopic visualization of bladder cancer is an essential method for initial bladder cancer detection and diagnosis, transurethral resection, and monitoring for recurrence. Researchers Aayush Aayush, Saloni Darji, Deepika Dhawan, Alexander Enstrom, Meaghan M. Broman, Muhammad T. Idrees, Hristos Kaimakliotis, Timothy Ratliff, Deborah Knapp, and David Thompson from Purdue University and Indiana University sought to develop a new intravesical imaging agent that is more specific and sensitive using a polypeptide based NIR (near-infrared) probe designed to detect cells bearing epidermal growth factor receptors (EGFR) that are overexpressed in 80% of urothelial carcinoma (UC) cases. The NIR imaging agent consisted of an elastin like polypeptide (ELP) fused with epidermal growth factor (EGF) and conjugated to Cy5.5 to give Cy5.5-N24-EGF as a NIR contrast agent. In addition to evaluation in human cells and tissues, the agent was tested in canine cell lines and tissue samples with naturally occurring invasive UC. “Dogs with naturally-occuring UC are an emerging option for a suitable large animal model of BC, where the cancer displays similar microscopic anatomy, histological appearance, biological behavior, heterogeneity, and molecular subtypes and markers to human invasive BC.” Full press release - https://www.oncotarget.com/news/pr/oncotarget-targeted-elastin-like-polypeptide-fusion-protein-for-near-infrared-imaging-of-human-and-canine-urothelial-carcinoma/ DOI: https://doi.org/10.18632/oncotarget.28271 Correspondence to: David Thompson – davethom@purdue.edu Keywords: bladder cancer, elastin-like polypeptide, NIR imaging, epidermal growth factor receptor (EGFR), translational studies About Oncotarget: Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, visit Oncotarget.com and connect with us: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
Listen to a blog summary of a recent research paper published by Oncotarget, entitled, "Immunotherapy Response Predicted by Machine Learning & Gut Microbiomes." __________________________________________ Immunotherapy has become a powerful breakthrough in cancer treatment, however, 50% of patients do not respond to immunotherapy. What internal or external features inhibit or confer patient or tumor response to immune system-harnessing therapeutics? These patient/tumor features that impact responsiveness to immunotherapy have yet to be fully elucidated. “Increasing evidence has emerged that gut microbial communities help shape the host immune system [9–11].” Full blog - https://www.oncotarget.org/2022/09/01/immunotherapy-response-predicted-by-machine-learning-gut-microbiomes/ DOI - https://doi.org/10.18632/oncotarget.28252 Correspondence to - Heidi H. Kong - konghe@mail.nih.gov Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632/oncotarget.28252 Keywords - gut microbiome; immunotherapy; 16S rRNA; machine learning; metagenomics About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit www.oncotarget.com and connect with us: SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube LinkedIn - www.linkedin.com/company/oncotarget Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a recent research paper published by Oncotarget, entitled, "Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma." __________________________________________ Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL) that is aggressive, difficult to treat and typically affects older adults. Recurrence and mortality rates among patients with MCL have remained high, despite recent therapeutic advances. Blastic mantle cell lymphoma (bMCL) is a rare subtype of MCL associated with a worse disease trajectory. “Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.” In previous studies, researchers reported that a combination of epigenetic and immunotherapy treatments may have synergistic activity and offer better outcomes in patients with MCL. In the current study, Francis R. LeBlanc, Zainul S. Hasanali, August Stuart, Sara Shimko, Kamal Sharma, Violetta V. Leshchenko, Samir Parekh, Haiqing Fu, Ya Zhang, Melvenia M. Martin, Mark Kester, Todd Fox, Jiangang Liao, Thomas P. Loughran, Juanita Evans, Jeffrey J. Pu, Stephen E. Spurgeon, Mirit I. Aladjem, and Elliot M. Epner from Pennsylvania State University College of Medicine, Penn State Hershey Cancer Institute, Winter Haven Hospital Cassidy Cancer Center, Icahn School of Medicine at Mount Sinai, National Cancer Institute, University of Virginia, UVA Cancer Center, University of Arizona College of Medicine, Oregon Health and Science University, and Beverly Hills Cancer Center used samples from a previous trial to perform correlative studies focused on clinical results in patients with blastic MCL. On August 16, 2022, their research paper was published in Volume 13 of Oncotarget, entitled, “Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma.” Full blog - https://www.oncotarget.org/2022/08/24/epigenetics-and-immunotherapy-combined-fights-rare-lymphoma/ DOI - https://www.oncotarget.com/article/28258/text/ Correspondence to - Francis R. LeBlanc - francis.leblanc@cchmc.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28258 Keywords - epigenetics, blastic mantle cell lymphoma, cladribine About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget on August 4, 2022, entitled, “Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.” Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. “Despite a number of new treatment options improving RCC patients' disease control rates and survival, the lack of useful biomarkers remains a major clinical concern.” In the current study, researchers Andliena Tahiri, Katarina Puco, Faris Naji, Vessela N. Kristensen, Glenny Cecilie Alfsen, Lorant Farkas, Frode S. Nilsen, Stig Müller, Jan Oldenburg, and Jürgen Geisler, from University of Oslo, Oslo University Hospital, Akershus University Hospital, and Pamgene International BV, performed protein tyrosine kinase (PTK) profiling using PamChip® technology. “The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib.” The results showed that 36 kinase substrates differ (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. Their assay showed that tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients. “The results of our study contribute to better understanding of the changes in kinase activity in RCC tumor cells involved in fundamental oncogenic cellular processes and the ex vivo effect of TKIs. We found tivozanib and cabozantinib to be more potent TKIs in RCC samples than sunitinib or pazopanib. The next step will be to correlate the efficacy and toxicity in individual patients with their respective kinase activity of normal and malignant kidney tissue.” DOI: https://doi.org/10.18632/oncotarget.28257 Correspondence to: Jürgen Geisler – Email: juergen.geisler@medisin.uio.no Keywords: kidney cancer, kinase activity, tyrosine kinase inhibitors, renal cell carcinoma, tyrosine kinase About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.