Podcasts about tyrosine kinase

Do you know how adverse events (AEs) associated with Bruton tyrosine kinase (BTK) inhibitors affect patients' lives and how best to manage these events? Credit available for this activity expires: 11/15/24 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/998369?ecd=bdc_podcast_libsyn_mscpedu

In this podcast, Xiuning Le from the University of Texas MD Anderson Cancer Center, Houston, TX, Eric Nadler from the Baylor University Medical Center, Dallas, TX, Daniel Costa from the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, and John Heymach from the University of Texas MD Anderson Cancer Center, Houston, TX discuss the use of EGFR tyrosine kinase inhibitors for the treatment of metastatic non-small cell lung cancer harboring uncommon EGFR mutations. This podcast is published open access in Targeted Oncology and is fully citeable. You can access the original published podcast article through the Targeted Oncology website and by using this link: https://link.springer.com/article/10.1007/s11523-023-00994-2 All conflicts of interest can be found online.   Open Access This podcast is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The material in this podcast is included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

This episode is sponsored is by BTG Pharmaceuticals Dr. Michael Bishop is an Assistant Member in the Solid Tumor Division of the Department of Oncology at St. Jude Children's Hospital in Memphis, TN. His clinical practice focuses primarily on the management of children and young adults with bone and soft tissue sarcomas, and his research interests are dedicated to the development of prospective clinical trials for the treatment of osteosarcoma. Dr. Bishop graduated from the University of Arkansas College of Medicine and completed his pediatric residency at Children's Mercy Kansas City, and fellowship in pediatric hematology and oncology at Cincinnati Children's Hospital Medical Center. Dr. Bishop is a member of the Children's Oncology Group Bone Tumor Committee and is the Study Chair for AOST2032, a prospective trial assessing the feasibility and efficacy of combining a multi-targeted tyrosine kinase inhibitor with chemotherapy for newly diagnosed osteosarcoma. --- What We Do at MIB Agents: PROGRAMS: End-of-Life MISSIONS Gamer Agents Agent Writers Prayer Agents Healing Hearts - Bereaved Parent and Sibling Support Ambassador Agents - Peer Support Warrior Mail Young Adult Survivorship Support Group EDUCATION for physicians, researchers and families: OsteoBites, weekly webinar & podcast with thought leaders and innovators in Osteosarcoma MIB Book: Osteosarcoma: From our Families to Yours RESEARCH: Annual MIB FACTOR Research Conference Funding multiple $100,000 and $50,000 grants annually for OS research MIB Testing & Research Directory The Osteosarcoma Project partner with Broad Institute of MIT and Harvard ... Kids are still dying with 40+ year old treatments. Help us MakeItBetter. https://www.mibagents.org​ Help support MIB Agents, Donate here https://give-usa.keela.co/embed/YAipuSaWxHPJP7RCJ SUBSCRIBE for all the Osteosarcoma Intel

CME credits: 1.00 Valid until: 20-06-2024 Claim your CME credit at https://reachmd.com/programs/cme/rationale-for-tyrosine-kinase-inhibitors-in-non-advanced-systemic-mastocytosis/15630/ Non-advanced systemic mastocytosis (nonAdvSM) is poorly understood and likely often overlooked or misdiagnosed. Multiple issues complicate the accurate differential diagnosis of nonAdvSM subtypes. Recent updates for diagnostic criteria, as well as validated assessments and a greater understanding of laboratory findings for this population, are providing practitioners with additional tools for arriving at an accurate diagnosis. Although many therapeutics exist for addressing symptoms of nonAdvSM, those treatments are purely palliative. To date, no disease-modifying drugs have been FDA-approved for treating nonAdvSM. However, therapeutics that are already approved for advanced SM or other indications are being evaluated in the nonAdvSM space. These drugs, particularly KIT inhibitors, have the potential to improve patient outcomes for nonAdvSM. Healthcare providers are in a unique position to improve patient outcomes by becoming experts in diagnosing, assessing, and monitoring patients with nonAdvSM; as well as ensuring access to the latest, most effective treatments. To that end, there is a need to increase disease state awareness and close knowledge gaps around the diagnosis and management of this rare disease.

Professor Karla Arruda and Professor Marcus Maurer discuss the development and implementation of UCARE in Brazil, and its potential benefits for individuals suffering from chronic spontaneous urticaria (CSU). The conversation extends towards exploring the framework of the Brazilian UCARE centres and projects, and how it can be implemented in other countries. Professor Maurer delves into the clinical efficacy, advantages, and impact on patient quality of life of utilising Bruton's tyrosine kinase inhibitors for the treatment of CSU, along with further discussion of alternative treatments. Access additional resources by signing up to Medthority and to be notified for future 'All Things Urticaria' podcast episodes!  Do you have suggestions for future episodes? Please visit UCARE to provide feedback via the link here and offer your suggestions for future topics and expert selection!

Please visit answersincme.com/BAV860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in neurology discusses Bruton's tyrosine kinase (BTK) inhibitors in relapsing multiple sclerosis (MS). Upon completion of this activity, participants should be better able to: Recognize the biologic rationale for therapeutically targeting BTK in MS; Describe the clinical impact of late-stage emerging BTK inhibitors in relapsing MS; and Outline clinical considerations for the future use of BTK inhibitors in the management of relapsing MS.

In our latest update, We discuss the results of a one year Phase I trial exploring the use of a tyrosinase inhibitor in an hydrogel implant for the treatment of neovascular AMD with Dr. Andrew Moshfeghi, Associate Professor of Ophthalmology, USC Roski Eye Institute.

Did you know there are 3 Bruton tyrosine kinase (BTK) inhibitors approved to treat chronic lymphocytic leukemia (CLL) in Europe? Credit available for this activity expires: 1/4/2024 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/986280?ecd=bdc_podcast_libsyn_mscpedu

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.27.522037v1?rss=1 Authors: Dos Santos, R. S., Guzman-Llorens, D., Perez-Serna, A. A., Nadal, A., Marroqui, L. Abstract: Aims/hypothesis: Type 1 diabetes is characterised by pancreatic islet inflammation and autoimmune-driven pancreatic beta cell destruction. Type I interferons, such as IFNalpha, are key players in early human type 1 diabetes pathogenesis, as the activation of the tyrosine kinase 2 (TYK2)-signal transducer and activator of transcription (STAT) pathway induces inflammation, a long-lasting MHC class I overexpression, endoplasmic reticulum (ER) stress, and beta cell apoptosis (in synergy with IL-beta). As TYK2 inhibition has been suggested as a potential therapeutic target for the prevention or treatment of type 1 diabetes, we investigated whether the selective TYK2 inhibitor deucravacitinib could protect beta cells against the damaging effects of IFNalpha and other proinflammatory cytokines (i.e. IFNgamma and IL-1beta). Methods: Inflammation, ER stress, and apoptosis were evaluated by real-time PCR, immunoblot, immunofluorescence, and nuclear dyes. The promoter activity was assessed by luciferase assay and insulin secretion and content by ELISA. All experiments were performed in the human EndoC-betaH1 cell line. Results: Pre-treatment with deucravacitinib prevented IFNalpha effects, such as STAT1 and STAT2 phosphorylation and protein expression as well as MHC class I hyperexpression, in a dose-dependent manner without affecting beta cell survival and function. Comparison between deucravacitinib and two Janus kinase inhibitors, ruxolitinib and baricitinib, showed that deucravacitinib blocked IFNalpha- but not IFNgamma-induced signalling pathway. Pre-treatment with deucravacitinib protected beta cells from the pro-apoptotic and proinflammatory effects of two different combinations of cytokines: IFNalpha + IL-beta and IFNgamma + IL-1beta. Moreover, this TYK2 inhibitor could partially revert apoptosis and inflammation in cells previously treated with IFNalpha + IL-1beta or IFNgamma + IL-beta. Conclusions/interpretation: Our findings suggest that, by protecting beta cells against the deleterious effects of proinflammatory cytokines without affecting beta cell function and survival, deucravacitinib could be repurposed for the prevention or treatment of early type 1 diabetes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode, we welcome the lead author of “Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A phase 2, Randomized, Double-Blind, Placebo-Controlled Trial” Dr. Eric Morand of Monash University. The objective of this multicenter clinical trial in lupus (recently published in “Arthritis & Rheumatology”) was to assess the efficacy of deucravacitinib in a phase II trial in adult patients with active lupus. Dr. Morand's methods, results and ultimate conclusions take center stage of our show today. 

Welcome to ACR Convergence 2022! Today, Dr. Vicki Shanmugam (host of ACR Journals on Air) joins Jon to tackle three, pivotal trials, that will be presented at our annual meeting this year! Join us as they dive into the objectives, the science behind them and their incredible results. You can find each one of the manuscripts discussed on this episode here: Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus Genicular Nerve Block for Pain Management in Patients With Knee Osteoarthritis: A Randomized Placebo-Controlled Trial  

Commentary by Dr. Iris Jaffe

Go online to PeerView.com/DTJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Bruton tyrosine kinase (BTK) inhibitors show great promise in the quest to identify additional novel interventions to address multiple sclerosis (MS) pathophysiology and help to individualize care. Four BTK inhibitors—evobrutinib, tolebrutinib, fenebrutinib, and remibrutinib—are in phase 3 clinical trials for relapsing and/or progressive MS, based on the potential of these agents to affect processes mediated by B cells and myeloid cells (eg, microglia), which may contribute to inflammation and neurodegeneration. At a recent live CME/NCPD/CPE event, a panel of expert physicians highlighted the rationale for using BTK inhibitors to treat MS, assessed the latest data from completed and ongoing clinical trials, and reviewed guideline-recommended protocols for patient imaging. In addition to the lively discussion, animated video abstracts further illustrated these topics. Upon completion of this activity, participants should be better able to: Describe the rationale for inhibiting Bruton tyrosine kinase (BTK) to treat multiple sclerosis (MS); Evaluate current evidence related to the efficacy, safety, and tolerability of BTK inhibitors in the treatment of MS; Identify patients who may benefit by treatment with BTK inhibitors, based on current evidence and individual treatment needs and priorities; and Implement guideline-recommended imaging protocols to assess disease activity and monitor treatment response in patients with MS.

Go online to PeerView.com/DTJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Bruton tyrosine kinase (BTK) inhibitors show great promise in the quest to identify additional novel interventions to address multiple sclerosis (MS) pathophysiology and help to individualize care. Four BTK inhibitors—evobrutinib, tolebrutinib, fenebrutinib, and remibrutinib—are in phase 3 clinical trials for relapsing and/or progressive MS, based on the potential of these agents to affect processes mediated by B cells and myeloid cells (eg, microglia), which may contribute to inflammation and neurodegeneration. At a recent live CME/NCPD/CPE event, a panel of expert physicians highlighted the rationale for using BTK inhibitors to treat MS, assessed the latest data from completed and ongoing clinical trials, and reviewed guideline-recommended protocols for patient imaging. In addition to the lively discussion, animated video abstracts further illustrated these topics. Upon completion of this activity, participants should be better able to: Describe the rationale for inhibiting Bruton tyrosine kinase (BTK) to treat multiple sclerosis (MS); Evaluate current evidence related to the efficacy, safety, and tolerability of BTK inhibitors in the treatment of MS; Identify patients who may benefit by treatment with BTK inhibitors, based on current evidence and individual treatment needs and priorities; and Implement guideline-recommended imaging protocols to assess disease activity and monitor treatment response in patients with MS.

Go online to PeerView.com/DTJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Bruton tyrosine kinase (BTK) inhibitors show great promise in the quest to identify additional novel interventions to address multiple sclerosis (MS) pathophysiology and help to individualize care. Four BTK inhibitors—evobrutinib, tolebrutinib, fenebrutinib, and remibrutinib—are in phase 3 clinical trials for relapsing and/or progressive MS, based on the potential of these agents to affect processes mediated by B cells and myeloid cells (eg, microglia), which may contribute to inflammation and neurodegeneration. At a recent live CME/NCPD/CPE event, a panel of expert physicians highlighted the rationale for using BTK inhibitors to treat MS, assessed the latest data from completed and ongoing clinical trials, and reviewed guideline-recommended protocols for patient imaging. In addition to the lively discussion, animated video abstracts further illustrated these topics. Upon completion of this activity, participants should be better able to: Describe the rationale for inhibiting Bruton tyrosine kinase (BTK) to treat multiple sclerosis (MS); Evaluate current evidence related to the efficacy, safety, and tolerability of BTK inhibitors in the treatment of MS; Identify patients who may benefit by treatment with BTK inhibitors, based on current evidence and individual treatment needs and priorities; and Implement guideline-recommended imaging protocols to assess disease activity and monitor treatment response in patients with MS.

Go online to PeerView.com/DTJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Bruton tyrosine kinase (BTK) inhibitors show great promise in the quest to identify additional novel interventions to address multiple sclerosis (MS) pathophysiology and help to individualize care. Four BTK inhibitors—evobrutinib, tolebrutinib, fenebrutinib, and remibrutinib—are in phase 3 clinical trials for relapsing and/or progressive MS, based on the potential of these agents to affect processes mediated by B cells and myeloid cells (eg, microglia), which may contribute to inflammation and neurodegeneration. At a recent live CME/NCPD/CPE event, a panel of expert physicians highlighted the rationale for using BTK inhibitors to treat MS, assessed the latest data from completed and ongoing clinical trials, and reviewed guideline-recommended protocols for patient imaging. In addition to the lively discussion, animated video abstracts further illustrated these topics. Upon completion of this activity, participants should be better able to: Describe the rationale for inhibiting Bruton tyrosine kinase (BTK) to treat multiple sclerosis (MS); Evaluate current evidence related to the efficacy, safety, and tolerability of BTK inhibitors in the treatment of MS; Identify patients who may benefit by treatment with BTK inhibitors, based on current evidence and individual treatment needs and priorities; and Implement guideline-recommended imaging protocols to assess disease activity and monitor treatment response in patients with MS.

Did you know that noncovalent BTK inhibitors are potentially the answer to the development of resistance to covalent BTK inhibitors? Credit available for this activity expires: 4/5/2023 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/971263?src=mkm_podcast_addon_971263

We discuss the DAVIO trial of EYP-1901 with Dr. Jay S. Duker, Chief Operating Officer of Eyepoint Pharmaceuticals.

Ok I change my mind, growth factors are the most amazing pieces in the human body bar none! We not only chat about growth factors but also look at Tyrosine Kinase Inhibitors as they work in the inhibition of how growth factors exhibit their work.

Listen to a soundcast of the October 29, 2021, FDA approval of Scemblix (asciminib) for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, previously treated with tyrosine kinase inhibitors, and for adult patients in chronic phase with the T315I mutation

Dr Nilima Parry Jones introduces the podcast for the Good Practice Paper: Management of cardiovascular complications of bruton tyrosine kinase inhibitors (BTKi). This good practice paper aims to help clinicians in recognising, understanding and appropriately managing cardiovascular complications of BTKi in order to optimise outcomes for patients. The podcast is to take the form of a question and answer session between Dr Renata Walewska and Professor Gregory Lip.   Dr Nilima Parry-Jones is a Consultant Haematologist at the Aneurin Bevan Local Health, Wales and an executive member of the UK CLL Forum. Dr Renata Walewska is a Consultant Haematologist at the Royal Bournemouth Hospital and Chair of the UK CLL Forum. Professor Gregory Lip is Price-Evens Chair of Cardiovascular Medicine at the University of Liverpool and Director of the Liverpool Centre for Cardiovascular Science and the University of Liverpool and Liverpool Heart & Chest Hospital.

Donald C. Moore, PharmD, BCPS, BCOP, DPLA, of Atrium Health, Levine Cancer Institute, in Concord, North Carolina, talks with host Wendy Vogel, MSN, FNP, AOCNP®, on recent data and strategies for managing adverse events of ibrutinib, acalabrutinib, and zanubrutinib in the treatment of B-cell malignancies. Related Content:A Review of the Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies. J Adv Pract Oncol 2021;12(4):439–447. https://doi.org/10.6004/jadpro.2021.12.4.8

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Sid and I am your host for episode #86 called Unit 4 Cell Communication and Cell Cycle: G Protein Receptors and Tyrosine Kinase Receptors. Segment 1: Introduction to G protein receptors and tyrosine kinase receptors G Protein receptors and tyrosine kinase receptors both work to mediate cell communication by binding a signaling molecule, which is also called a ligand. Then this signal is sent through a transduction pathway where the last target protein causes some response. The response for both can be a variety of things such as gene expression, apoptosis, metabolic responses, cell division, or cell growth. Despite being similar in this way, g protein receptors and tyrosine kinase receptors work in very different ways Segment 2: More About G protein receptors Let's start by discussing g protein receptors. G proteins are very diverse and can bind to many different signals. One example is odorant (or scent) receptors. G proteins receptors are located in the cell membrane which is where an extracellular ligand binds to it. The signal is eventually sent to a g protein which is located on the membrane, but on the cytoplasmic side. Before the G protein is activated, GDP is bound to it which keeps it inactive. GDP is guanosine diphosphate. After the signal binds to the receptor, the receptor slightly changes shape and becomes active. Then, the GDP binds to the g protein receptor. Since the G protein no longer has a GDP bound to it, it frees it up to accept and bind to GTP. The GTP activates the G protein. The G protein is made up of three subunits: alpha, beta, and gamma. When the GTP is bound to the G protein and activates it, the alpha subunit detaches and moves away from the receptor. Now the G protein is split into two parts: one part is the single alpha subunit and the other is the beta and gamma subunits. These two parts can go on to interact with other proteins and cause a transduction pathway that results in one of many responses. Eventually, the alpha subunit comes back and hydrolyzes the GTP which keeps the G protein active and changes it back into GDP. At this point the G protein will once again become inactive. G proteins coupled receptors are very important in the human body. Disruptions can cause diseases like cystic fibrosis or cholera.  Now let's talk about tyrosine kinase receptors. Tyrosine kinase receptors are enzyme linked receptors. Enzyme linked receptors are receptors that are associated with an enzyme. A kinase is a protein that phosphorylates other proteins. For tyrosine kinase receptors, the kinase phosphorylates tyrosine. To start the process, a signalling molecule attaches to two tyrosine kinase receptors. These come together and form a dimer. Then, each tyrosine kinase receptor phosphorylates the domains of the tyrosine kinase receptor. Then, once the tyrosine is phosphorylated, it can send signals to other molecules Segment 3: Connection to the Course G protein receptors and tyrosine kinase receptors are very important to many species. Problems with g protein receptors can cause choler, cystic fibrosis, and some bacterial infections. Problems with tyrosine kinase receptors can also cause diseases and cancers. Both of these receptors play integral parts in many different species. This can be evidence of the endosymbiotic theory. Since so many species use these receptors, they likely came from a common ancestor and had an evolutionary advantage. Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com).  Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcast...

Interview with Ehab Atallah, MD, author of Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial

Interview with Ehab Atallah, MD, author of Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial

Pillai explains how earlier in his career he discovered that two surrogate light chains bind to the heavy chain in pre-B cells to create the pre-B cell receptor (pre-BCR). He showed that binding of the surrogate chains facilitates the formation of the pre-BCR that is needed for B cell development. Pillai demonstrated that the pre-BCR signals through Bruton Tyrosine Kinase (Btk). Patients with non-functional Btk manifest signs of immunodeficiency and deficiency of B-cells in the blood, which shows the importance of pre-BCR signaling for proper B-cell development.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.246454v1?rss=1 Authors: Schmalohr, B. F., Mustafa, A.-H. M., Krämer, O., Imhof, D. Abstract: Janus kinase 2 (JAK2) is the most important signal transducing tyrosine kinase in erythropoietic precursor cells. Its malfunction drives several myeloproliferative disorders. Heme is a small metal ion-carrying molecule, which is incorporated into hemoglobin in erythroid precursor cells to transport oxygen. In addition, heme is a signaling molecule and regulator of various biochemical processes. Here we show that heme exposure leads to hyperphosphorylation of JAK2 in a myeloid cancer cell line. Two peptides identified in JAK2 represent heme-regulatory motifs and show low micromolar affinities for heme. These peptides map to the kinase domain of JAK2, which is essential for downstream signaling. We suggest these motifs to be the interaction sites of heme with JAK2, which drive the heme-induced hyperphosphorylation. The results presented herein may facilitate the development of heme-related pharmacological tools to combat myeloproliferative disorders. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.13.093617v1?rss=1 Authors: Kamitakahara, A. K., Ali Marandi Ghoddousi, R., Lanjewar, A. L., Magalong, V. M., Wu, H.-H., Levitt, P. Abstract: The vagal motor nucleus ambiguus (nAmb) innervates the intrinsic muscles of the larynx, providing direct motor control over vocal production in humans and rodents. Here, we demonstrate that early developmental signaling through the MET receptor tyrosine kinase (MET) is required for proper formation of the nAmb. Embryonic deletion of Met in the developing brainstem resulted in a loss of one-third of motor neurons in the nAmb. While the remaining neurons were able to establish connections with target muscles in the larynx, advanced signal processing analyses revealed severe deficits in ultrasonic vocalization in early postnatal life. Abnormal vocalization patterns persisted into adulthood in the majority of mice tested. Interestingly, 28% of adult mice recovered the ability to vocalize demonstrating heterogeneity in circuit restitution. Together, the data establish MET as a factor necessary for development of a specific subset of neurons in the nAmb required for normal ultrasonic vocalization. Copy rights belong to original authors. Visit the link for more info

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Emerging ‘Tumour-Agnostic' Oncology Treatment: The Role of the Pathologist in Identifying Neurotrophic Tyrosine Kinase Gene Fusions

Dr Mahon presents data at ASH 2016 with an update from the EURO-SKI trial of TKI cessation for myeloid leukaemia patients.

Dr Richter presents, at a press conference at EHA 2016, the results of the EURO-SKI trial which sought to determine the proportion of patients keeping their therapy response after stopping TKIs and to the clinical and biological factors that predict successful TKI-stop. Results of the trial show that 62% of the patients still maintained treatment response (MMR) 6 months after stopping therapy.

Stuart Yuspa explains how increased signaling through the tyrosine kinase receptor MET promotes squamous cell carcinoma.

Dr Middleton talks to ecancertv at EADO 2015 about combining immunotherapies and targeted therapies in melanoma. Should we be using anti-PD1 or tyrosine kinase inhibitors to treat patients?

Prof Branford (Adelaide University Adelaide, Australia) talks to ecancertv at EHA 2015 about differences in molecular responses to tyrosine kinase inhibitors in chronic myeloid leukaemia and how decisions can be made about stopping the treatment.

Prof Deininger talks to ecancertv at ASH 2013, New Orleans. Protein tyrosine kinases (PTKs) regulate cell growth and other key functions. Constitutive PTK activation by somatic mutations, overexpression, or abnormal upstream signaling is characteristic of many cancers, including hematologic malignancies, providing a rationale for therapeutically targeting PTKs with small molecules. Despite shortcomings, TKIs have completely changed the face of CML. Unfortunately, repeating this success in other hematologic malignancies has been challenging, likely reflecting differences in disease biology as much as suboptimal design of early compounds. CML-CP represents one extreme of the spectrum, where a single genetic lesion is sufficient to produce the phenotype and the hierarchy of hematopoietic differentiation is maintained. The situation is different in acute myeloid leukemia (AML) with activating FLT3 mutations. Not only these AML cases have mutations in other genes, they typically acquire FLT3 mutations late during disease evolution, implying that the disease-initiating clone will be impervious to FLT3 inhibition. Progress has been made through successive development of more potent TKIs with improved pharmacology, leading to quizartinib. From the target perspective, it is likely that most activated kinase alleles have been discovered and the focus should shift to identification of disease-critical unmutated kinases. Lastly, identifying synthetically lethal inhibitor combinations will be critical to fully exploit the potential of TKI therapy.

Wed, 18 Sep 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16135/ https://edoc.ub.uni-muenchen.de/16135/1/Gatto_Graziana.pdf Gatto, Graziana ddc:570, dd

The tyrosine kinase BMX may act as a global promoter of maximal receptor tyrosine kinase activity.

Only one treatment is licensed for idiopathic pulmonary fibrosis and this only in Europe. Luca Richeldi (Center for Rare Lung Diseases, University of Modena, Italy) describes his phase 2 trial of a tyrosine kinase inhibitor to see if it could be safely and effectively used in patients with the disease. Dr Richeldi’s research was published in the New England Journal of Medicine.See also:http://www.nejm.org/doi/full/10.1056/NEJMoa1103690

Background: Everolimus is approved for treatment of anti-vascularendothelial growth factor (VEGF)-refractory patients with metastaticrenal cell carcinoma (mRCC). Clinical trials rarely mirror treatmentreality. Thus, a broader evaluation of everolimus is valuable forroutine use. Patients and Methods: A German multicenternon-interventional study documented mRCC patients starting everolimusafter failure of initial VEGF-targeted therapy. Primary endpoint waseffectiveness, defined as time to progression (TIP) according toinvestigator assessment (time from first dose to progression). Results:Of 382 documented patients, 196 were included in this interim analysis.

This multidisciplinary presentation, part of the Tumor Board Series on ASCO University (http://university.asco.org) presents a case study of a patient with a history of coronary artery disease who is diagnosed with renal cell carcinoma and treated with a tyrosine kinase inhibitor.

Receptor tyrosine kinases existed in the unicellular ancestors of multicellular animals and underwent diversification in the metazoan lineage.

Patients with epidermal growth factor receptor (EGFR) gene mutations should receive EGFR tyrosine kinase inhibitors as 1st line therapy because they produce higher response rates, long progression free survival, reduced toxicity, improved symptom control and convenience of oral administration compared to chemotherapy doublets.

October highlights, including discussion of the trial about the tyrosine kinase ALK and non-small-cell lung cancer.

Dr. Lecia Sequist of Massachusetts General Hospital presents a summary of the challenge of acquired resistance to EGFR tyrosine kinase inhibitors like Tarceva (erlotinib) and Iressa (gefitinib), along with emerging ideas for overcoming it.

Dr. Lecia Sequist of Massachusetts General Hospital presents a summary of the challenge of acquired resistance to EGFR tyrosine kinase inhibitors like Tarceva (erlotinib) and Iressa (gefitinib), along with emerging ideas for overcoming it.

Runtime 40:38 Physician-scientist, Ross Levine, discusses how the study of genomic techniques can lead to the development of new treatments. read more

Enhanced Audio PodcastAired date: 2/23/2009 12:00:00 PM Eastern Time

Enhanced Video PodcastAired date: 2/23/2009 12:00:00 PM Eastern Time

Science-Oriented DLS from Jan 14, 2009

LungCancerUpdate.com/ThinkTank – Proceedings from a Clinical Investigator “Think Tank.” EGFR Tyrosine Kinase Inhibitors. Interviews conducted by Neil Love, MD. Produced by Research To Practice.

Background: During inflammation, beta(2)-integrins mediate leukocyte adhesion to the endothelium accompanied by the activation of the spleen tyrosine kinase Syk. Results: We investigated leukocyte adhesion and rolling in cremaster muscle venules before and during stimulation with fMLP using mice with a Syk(-/-) hematopoietic system. In unstimulated venules, Syk(-/-) leukocytes adhered less efficiently than control leukocytes while rolling was similar between Syk(-/-) and control leukocytes. During fMLP-superfusion, control mice showed significantly increased adhesion accompanied by reduced rolling. For Syk(-/-) leukocytes, an increase in adhesion with a concomitant decrease in rolling was only observed during the first three minutes during fMLP stimulation, but not at later time points. We also investigated leukocyte spreading against the vessel wall during fMLP stimulation and found a significant impairment of spreading for Syk(-/-) leukocytes. Additional in vitro experiments revealed that the adhesion and spreading defect seen in Syk(-/-) chimeric mice was due to compromised beta(2)-integrin-mediated outside-in signaling. Conclusion: We provide substantial evidence for an important role of Syk in mediating beta(2)-integrin dependent outside-in signaling leading to sustained leukocyte adhesion and spreading during the inflammatory response in vivo.

Fri, 13 Feb 2004 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/1799/ https://edoc.ub.uni-muenchen.de/1799/1/Fischer_Oliver_M.pdf Fischer, Oliver Martin ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Background: Tripe palms is a descriptive term for a cutaneous paraneoplastic keratoderma. Tripe palms are frequently associated with gastric and pulmonary carcinoma. The pathogenetic mechanism remains unknown. Objective: To determine the influence of receptor tyrosine kinases, which are both expressed in pulmonary carcinomas and in human skin, we performed expression studies on epidermal growth factor receptor (EGFR), HER2, HERS in a skin sample of tripe palms obtained from a patient with non-small-cell lung cancer with lymph node involvement. Two months after diagnosis, the patient had developed palmoplantar `tripe palms'. Additionally, the expression of SRC, c-myc and p16/CDKN2 were studied. Method: Conventional reverse-transcription polymerase chain reaction was performed on a tissue sample of tripe palms. Results: Weak expression of HER2 and of p16/CDKN2 was found. EGFR, HERS, c-myc and SRC were not expressed. Conclusion: Receptor tyrosine kinases of subclass I, the tyrosine kinase SRC and the oncogene c-myc play no major role in the pathogenesis of this case of tripe palms. Copyright (C) 2000 S. Karger AG. Basel.

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.

Go online to PeerView.com/NXB860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Growing appreciation of the importance of B-cell–targeted therapies in multiple sclerosis (MS) management has spurred research into the potential role that Bruton tyrosine kinase (BTK) inhibitors may play in MS management. In this activity, based on a recent live satellite symposium, expert faculty will put BTK inhibitors into context, starting with the expanding understanding of the inflammatory and neurodegenerative processes of MS, the roles of B cells, microglia, and T cells, and how the ongoing investigations of BTK inhibitors as possible MS treatments build upon the successes of B-cell–targeted therapies. They will also review the evidence related to current clinical trials and engage learners in a case-based discussion exploring how BTK inhibitors might someday be deployed to address unmet needs of individuals with MS. Upon completion of this CE activity, participants will be able to: Recognize characteristics and evidence related to the role of BTK inhibitors in addressing MS pathophysiology, Compare characteristics of BTK inhibitors with other B-cell–targeted therapies, Evaluate available data on the efficacy, safety, and tolerability of BTK inhibitors in the context of addressing the treatment needs of patients with MS.