ACS Research - TheoryLab

Inflammatory breast cancer (IBC) is rare and accounts for only 1% to 5% of all breast cancers, but it is considered an aggressive cancer because it grows quickly and is more likely to come back after treatment than other types of breast cancer. It causes symptoms of breast inflammation like swelling and redness, which is caused by cancer cells blocking lymph vessels in the skin causing the breast to look "inflamed." Gayathri R. Devi, PhD, is a two-time American Cancer Society grantee who recently received a Mission Boost Grant to “boost” her inflammatory breast cancer research and move it closer to patients. Dr. Devi joined the podcast to talk about risk factors for IBC, how it's different from other breast cancer types, and recent advances in her lab with promising clinical implications. Dr. Devi is Program Director for the Duke Consortium for Inflammatory Breast Cancer, Associate Professor of Surgery and Pathology at Duke School of Medicine, and the Director of the Duke North Carolina Central University bridge office as part of the Duke School of Medicine Clinical and Translational Sciences Institute. 3:18 – The symptoms and signs of inflammatory breast cancer (IBC) 6:34 – How inflammatory breast cancer differs from other, more common breast cancers 9:36 – Risk factors for inflammatory breast cancer 14:22 –Instead of a single tumor mass, IBC patients have small groups of tumor cells called emboli found in the breast, skin and lymph nodes around the breast tissue. What are emboli? How do they form? 16:00 – Why do emboli form in this way? 18:51 – What makes these emboli resistant to treatment and able to spread? 21:43 – On her ACS-funded research, which focuses on the environment in which the IBC emboli form, in the breast. Why is the breast environment so important? 28:35 – Adaptive stress response 31:15 – “I'll give you an example here and talk a little about our research findings that are clinically relevant.” 38:25 – How do we target inflammatory breast cancer therapeutically? 40:47 – The 3M approach: Models, Mechanisms, and Measures 45:30 – If she could wave a magic anti-IBC wand, where would we be in 5 years? 48:27 – The impact that ACS funding has had on this area of research 49:54 – “Another very important distinction about ACS…” 51:47 – How inflammatory breast cancer recently affected her family

The first few minutes of this conversation is for a lay audience, as Elham Azizi, PhD, and Charly Good, PhD, explained how they're investigating what causes cancer to grow and spread and how to improve immunotherapy. Then the discussion moved toward a scientific audience, as Drs. Azizi and Good shared recent findings and asked probing questions about future directions and opportunities in cancer research. Elham Azizi, PhD, is a former American Cancer Society postdoctoral fellow who is now an Assistant Professor of Biomedical Engineering at Columbia University. She joined the podcast to share findings from her recent publication, “Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy” (https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01471-6#secsectitle0020). Charly Good, PhD, is an American Cancer Society postdoctoral fellow in the lab of Shelley Berger, PhD, at the University of Pennsylvania. She recently published research in Cell on “An NK-like CAR T cell transition in CAR T cell dysfunction” (https://www.cell.com/cell/fulltext/S0092-8674(21)01331-3). FOR A GENERAL AUDIENCE 1:25 – Dr. Azizi explains how her lab uses machine learning techniques and other cutting-edge technologies to understand what's happening in the tumor microenvironment 2:47 – Dr. Good describes the focus of her research—using the patient's own immune system to attack cancer FOR A SCIENTIFIC AUDIENCE 4:19 – Dr. Good describes takeaways from her recent publication on “An NK-like CAR T cell transition in CAR T cell dysfunction” (https://www.cell.com/cell/fulltext/S0092-8674(21)01331-3) 7:25 – Dr. Azizi reacts to the paper… 8:51 – …and asks why some patients didn't see an increase in NK receptor expression 12:22 – Dr. Azizi shares findings from her paper, “Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy” (https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01471-6#secsectitle0020) 17:40 – Dr. Good asks: “Was it at all surprising to you when you first realized that the exhausted population was specific to the responders pre-infusion?” 22:10 – What's next in machine learning? 26:03 – On the impact of ACS funding on their research 30:26– Why it's an exciting time for cancer research

Corinne Leach, PhD, MPH, MS, who leads cancer survivorship research at the American Cancer Society, joined the podcast to discuss her recent publication on the rise of mental health distress during the COVID-19 pandemic. Using data from the American Cancer Society Cancer Prevention Study-3 (CPS-3) cohort, Dr. Leach and collaborators “identified factors associated with increased depression and anxiety during the pandemic, including sociodemographic characteristics, stressors, and comorbid conditions associated with increased risk for poor COVID-19 outcomes.”* They also presented findings related to financial stressors and looked at long-term implications. For resources and information to help you cope during and after cancer treatment, please visit: https://www.cancer.org/treatment/survivorship-during-and-after-treatment.html Dr. Leach is Senior Principal Scientist of Behavioral Research in the Population Sciences group at the American Cancer Society. She serves as the Principal Investigator of the American Cancer Society (ACS) survivorship cohorts, including the Studies of Cancer Survivors and the Cancer Survivor Transition Study. 3:13 –Pandemic-related stressors that have been associated with greater levels of anxiety and depression 8:09 – Her recent study on how our mental and physical health prior to the pandemic factored into our ability to deal with the psychological stress of the pandemic 10:57 – On long-term implications for mental health 12:45 – A snapshot of what cancer survivorship looks like in the United States 15:09 – On similarities between cancer survivors and participants her your study whose stressors were associated with anxiety and depression 17:25 – On post-treatment programs for cancer survivors 21:51 – Helpful ways to deal with significant life stressors * http://pressroom.cancer.org/StressorsPandemicPredictors

People going through cancer treatment sometimes have cognitive changes such as trouble remembering, paying attention, or thinking clearly. Drs. Judith Carroll and Kathleen Van Dyk are clinician scientists who help patients with cancer-related cognitive impairment and conduct research into what causes it, how to identify patients at risk for it, and how to reverse its effects. Judith Carroll, PhD, is Associate Professor in the Department of Psychiatry and Biobehavioral Science at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, and she's the term Endowed Chair of the George F. Solomon Professorship in Psychobiology at UCLA. She's also a Member of the Cousins Center for Psychoneuroimmunology. She received American Cancer Society funding to support her research on “Biobehavioral Vulnerability to Accelerated Aging In Breast Cancer Survivors” from 2016-2020. Kathleen Van Dyk, PhD, is Assistant Professor in the Department of Psychiatry and Biobehavioral Science at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, and she's a practicing neuropsychologist. She was an American Cancer Society postdoctoral fellow, studying “Cognitive Decline in Breast Cancer Survivors,” from 2017-2019. INCIDENCE AND NATURE OF THE PROBLEM 2:09 – What is “cancer-related cognitive impairment?” Is it the same as “chemo brain?” 3:12 – How common is it? 4:41 – What kind of symptoms does it produce? CONTRIBUTING FACTORS AND MECHANISMS 6:54 – Is cancer-related cognitive impairment a side effect of cancer? Is it caused by certain treatments? 12:11 – How has COVID impacted cognitive impairment among breast cancer survivors? 14:22 – On the biology of aging and how cancer could accelerate the aging process TREATMENT 17:48 – Is cancer-related cognitive impairment reversible? 22:04 – On the exciting potential of sleep interventions 23:54 – Understanding the effects of endocrine therapies on brain function CLOSING THOUGHTS 25:42 – How ACS funding has impacted their career and research 29:40 – A message they'd like to share with cancer patients, survivors, and caregivers who are concerned about cancer-related cognitive impairment

In this episode of the TheoryLab podcast, two American Cancer Society grantees discussed key takeaways from their recent publications. In the first part of the conversation, which is intended for a lay audience, Dr. Joshua Andersen and Dr. Bhuminder Singh talked about targeted therapies, treatment side effects, and drug resistance. Then they moved into a more technical discussion of their recent papers. Dr. Andersen recently published findings showing that “TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.” https://doi.org/10.1038/s41467-021-25622-3 Dr. Singh published a study recently showing that “Induction of apically mistrafficked epiregulin disrupts epithelial polarity via aberrant EGFR signaling.” https://doi.org/10.1242/jcs.255927 Joshua L. Andersen, PhD, is Associate Professor of Biochemistry at Brigham Young University. He is a two-time American Cancer Society grantee. Bhuminder Singh, PhD, is Assistant Professor of Medicine and Cell and Developmental Biology at Vanderbilt University Medical Center, and he is also a two-time American Cancer Society grantee. 1:25 – Dr. Andersen explains why his lab is focused on improving targeted therapies 2:31 – Dr. Singh describes how his research is focused on addressing drug resistance in colorectal cancer 4:28 – Dr. Andersen dives into his lab's new Nature Communications paper on a new cancer driver—"it's been probably the most rewarding project that I've been a part of in my career” 8:11 – Dr. Singh asks a few questions about the paper: “Are there any mutations in TNK1 in human cancer?” 10:01 – What ubiquitinated proteins was it binding to? 11:44 – Is TNK1 itself ubiquitinated in certain conditions? 12:49 – Dr. Singh explains takeaways from his paper, “Induction of apically mistrafficked epiregulin disrupts epithelial polarity via aberrant EGFR signaling” 19:16 – Follow-up questions from Dr. Andersen: “How could the mistrafficking of a single ligand affect its localization so dramatically?” 22:04 – “That has to send a signal then to start trafficking the intracellular EGFR out to the apical side of the cell, right?” 27:49 – “As someone who hasn't really thought about cell polarity very much inside a solid tumor, what would be the effects of mistrafficking in terms of the architecture of a solid tumor?” 31:18 – The impact of American Cancer Society funding on their research

When a cancer patient has a serious diagnosis, clinicians and families can struggle with how patients experience hope. Three distinguished palliative care physicians and researchers joined the podcast for a conversation about their recent paper in JAMA titled, “Holding Hope for Patients with Serious Illness” (https://jamanetwork.com/journals/jama/article-abstract/2784454). Drs. Abby Rosenberg, Robert Arnold, and Yael Schenker shared their own experiences treating seriously ill patients and talked about how we can navigate the tension between appreciating the potential therapeutic benefit of hope and being concerned about perceived unrealistic hopes: “Rather than being concerned that hope is either so fragile that it can be lost, or so powerful that it can overwhelm decision making, clinicians should remember that hope is protective, if not necessary, for managing serious illness. Holding complex, flexible, and diverse hopes enables patients to believe in the unlikely while simultaneously accepting the inevitable. The role of clinicians is to support both.” Abby Rosenberg, MD, MS, MA, is a pediatric oncologist and palliative care physician and researcher at the University of Washington, where she directs the pediatrics component of the Cambia Palliative Care Center, and Seattle Children's Research Institute, where she directs the Palliative Care and Resilience Lab. She has an American Cancer Society Research Scholar Grant to study “Resilience Outcomes Among Adolescents and Young Adults with Advanced Cancer.” Robert M. Arnold, MD, is a palliative care physician, Distinguished Professor of Medicine, and Chief of the Palliative Care Section at the University of Pittsburgh. He previously served as a member of the American Cancer Society's palliative care peer review committee. Yael Schenker, MD, MAS, is a palliative care physician, Professor of Medicine, and Director of the Palliative Research Center (PaRC) at the University of Pittsburgh. She is a past recipient of American Cancer Society research funding, which supported her study of “Primary Palliative Care for Patients with Advanced Hematologic Malignancies.” 3:27 - The therapeutic benefit of hope and why it's helpful to patients and caregivers 5:12 – Why clinicians sometimes feel the need to “correct” a patient's hope 8:56 – How physicians can address the tension of appreciating the potential therapeutic value of hope but being concerned about perceived unrealistic hopes 10:50 – On how physicians can help patients diversify and increase their hopes 6:24 – How they became interested in this topic and decided to explore this topic in a broader way 17:35 – Advice they would share with someone in medical school who might someday treat patients with a poor prognosis 19:03 – A message for caregivers of a patient with a terminal illness

Lung cancer is the leading cause of cancer death among both men and women in the United States and worldwide. Small cell lung cancer comprises 15-17% of lung cancer cases, and it is the most aggressive subtype of lung cancer, growing rapidly and spreading to other organs quickly. Luke Hoeppner, PhD, received American Cancer Society funding to test whether therapeutically targeting a specific molecular pathway inhibits small cell lung cancer growth. Dr. Hoeppner's lab was the first to report that activation of this particular pathway, called dopamine signaling, inhibits other forms of lung cancer growth. By therapeutically altering the dopamine signaling pathway, he hopes to inhibit small cell lung cancer progression and drug resistance, facilitating further advancement to new treatments. For more information about lung cancer, visit https://www.cancer.org/cancer/lung-cancer.html. Luke Hoeppner, PhD, is Assistant Professor and leader of the Cancer Biology research section at The Hormel Institute, University of Minnesota. 5:09 – What is small cell lung cancer? What vital statistics about it should we know? 5:57 –What is the standard therapy for small cell lung cancer patients? 8:13 – Why is it so hard to treat? 10:04 – “Another way to put it is…” 13:59 – Why drug resistance is such an important area of research for small cell lung cancer 15:42 – “We're trying to focus on understanding what in particular small cell lung cancer cells are doing to evade chemotherapy, and is there a combination treatment that we could add to chemotherapy that would prevent (resistance)?” 16:18 – On his lab's novel approach to combatting resistance 24:17 – What are the therapeutic implications? 25:05 – Why he's optimistic about this line of research 26:31 – On how American Cancer Society funding has impacted his research 27:18 – A message he'd like to share with cancer patients, survivors, and caregivers

According to American Cancer Society researchers, in the United States in 2021, there will be an estimated 281,550 new cases of invasive breast cancer diagnosed in women.* Finding breast cancer early and getting state-of-the-art cancer treatment are the most important strategies to prevent deaths from breast cancer. Breast cancer that's found early, when it's small and has not spread, is easier to treat successfully. Getting regular screening tests is the most reliable way to find breast cancer early. The American Cancer Society has screening guidelines for women at average risk of breast cancer, and for those at high risk for breast cancer: https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html. Two breast cancer researchers joined the podcast to discuss screening for the early detection of breast cancer. Anne Marie McCarthy, PhD is a cancer epidemiologist and assistant professor at the University of Pennsylvania's School of Medicine. She is the recipient of an American Cancer Society Research Scholar Grant to fund her research into “A Precision Medicine Approach to Breast Cancer Early Detection.” Lauren Teras, PhD, is a senior scientific director of epidemiology research in the Population Science team at the American Cancer Society. 7:43 – Important things to know about breast cancer risk 9:55 – Why mammography is recommended for all women - “Any woman that has breasts should think about screening for breast cancer with mammography on a regular basis” 12:50 – But mammography screening isn't necessarily enough for all women 18:26 – On the challenges of mammography screening and aggressive cancers 23:21 – On the association of breast density with cancer risk 26:48 – Women who could benefit from more intensive screening 29:46 – On being the best advocate for yourself (What do recommendations and high-risk categories mean for an individual?) 34:45 – A message for breast cancer patients, survivors, and caregivers 35:56 – The impact of American Cancer Society funding on Dr. McCarthy's research * https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf

“More than 50% of cancer survivors report problems paying medical bills, financial distress, or delaying and/or forgoing medical care in the past year.”* The financial burden of cancer can affect survivors for years. And it can affect anyone: a cancer diagnosis as a young adult can have financial ramifications that can change the course of a person's life; a diagnosis for someone who's retired and on a fixed income can pose problems that nobody should have to face. The cost of cancer treatment also deepens disparities—not everyone can afford the most effective treatments. Stacie Dusetzina, PhD, and Robin Yabroff, PhD, are two of the leading voices on research on the financial burden of cancer. They joined the podcast to discuss prescription drug coverage in America, problems that cause financial challenges for people with and without insurance, and potential policy solutions. Stacie Dusetzina, PhD, is Associate Professor in the Department of Health Policy and an Ingram Associate Professor of Cancer Research at Vanderbilt University. Robin Yabroff, PhD, is the Scientific Vice President of Health Services Research in the Surveillance and Health Equity Science team at the American Cancer Society. *Yabroff, K.R., Zhao, J., Han, X. et al. Prevalence and Correlates of Medical Financial Hardship in the USA. J GEN INTERN MED 34, 1494–1502 (2019). https://doi.org/10.1007/s11606-019-05002-w 2:12 – Pain points in prescription drug coverage for Americans – for infusion therapies… 7:39 – …and for orally administered therapies 12:24 – Why it can be hard to predict financial toxicity 13:48 – An example that hits close to home – a metastatic breast cancer patient with Medicare Advantage 17:33 – The financial implications of being diagnosed with cancer when young…of paying for cancer therapies when retired and on a fixed income…and of dealing with the costs of chronic illness 22:42 – Solutions! “The most obvious one to me is fixing the Medicare Part D policy to limit total out-of-pocket spending…” https://www.nejm.org/doi/full/10.1056/NEJMp2027580 25:34 – Ways to reduce the burden of high deductible plans 27:54 – “Despite how dire the situation you describe is, it's actually worse.” How new advances in treatment will worsen cancer disparities unless we take action 29:30 – Evidence showing that Medicaid expansion helps, but “making care affordable is going to take a lot more than Medicaid expansion” 31:11 – “We've got to stop paying for the stuff that doesn't work if we want to have better coverage for the stuff that does work.” 37:04 – Why cancer prevention strategies are key 39:00 – Advice for newly diagnosed cancer patients and their families for dealing with the financial cost of cancer

The St. Baldrick's Foundation, the largest charitable funder of childhood cancer research grants, and the American Cancer Society, a health organization dedicated to eliminating cancer, formed a partnership in 2019 to fund grants that will accelerate childhood cancer research with the goals of understanding and discovering new treatment options and improving care and survival in children with cancer. Kathleen Ruddy, St. Baldrick's Foundation CEO, joined the podcast to talk through the goals of this unique partnership. “Why do some patients respond better than others to a particular treatment? Why does one treatment cause more late effects than another? What else can we learn to speed up progress, to cure more children, more effectively, and less harshly?” Then two of the grantees who have been funded through the partnership talked about what they hope to accomplish. Yael P. Mossé, MD, is Associate Professor of Pediatrics at the University of Pennsylvania and Director of the Neuroblastoma Developmental Therapeutics Program, as well as a pediatric oncologist at The Children's Hospital of Philadelphia. Dr. Mossé's grant is focused on improving patient outcomes for ALK mutant neuroblastoma through precision molecular targeting. E. Anders Kolb, MD, is Vice Chairman for Research and Professor in the Department of Pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University, as well as Director of the Nemours Center for Cancer and Blood Disorders at Nemours/Alfred I. duPont Hospital for Children. Dr. Kolb's study aims to validate the detection of novel biomarkers for the Pediatric Acute Leukemia (PedAL) Initiative Sub-trials. 0:00 – Kathleen Ruddy, CEO of St. Baldrick's Foundation 10:25 – Yael P. Mossé, MD, and E. Anders Kolb, MD 11:29 – Drs. Mossé and Kolb on why, “in pediatric cancer care, clinical trial participation is the standard of care” 13:31 – Dr. Mossé on how her team is “bringing the science to the patient” to learn how children with neuroblastoma respond (or don't respond) to treatments 15:57 – Dr. Kolb on why it's so important, and challenging, to bring precision medicine approaches to childhood cancer treatment 18:37 –Dr. Mossé explains the goal “to bring the science to the clinical trials in real time and not for there to be a lag” 21:38 – Dr. Kolb highlights how revolutionary it is for Dr. Mossé to change a clinical trial based on data emerging in the lab 23:26 – Dr. Kolb explains how “the AML that kids get is nothing like the AML that older adults get” and why this matters for drug development 27:43 – “We as pediatricians are taught early on,” notes Dr. Mossé, “that kids are not small adults, and it really is the same for pediatric cancer.” 30:17 – Dr. Kolb on the inspiration he drew from an initiative by St. Baldrick's Foundation called Project:EveryChild, and describes his new study: “what we hope is that we will be as successful in relapse as we have been in newly diagnosed AML” 32:25 – Dr. Mossé on the value of collecting tissue over time, including at relapse, and how a major part of her new study is using liquid biopsies to collect samples in a less invasive way 34:43 – Dr. Kolb on the impact of this funding: “If we're successful, we're going to be able to rapidly screen for relevant biomarkers and we're going to be able to enroll kids in the therapy that has the highest potential to provide benefit.” 37:46 – Dr. Mossé describes how this funding will support her research: “My hope and my expectation is to make a really big difference for a small subset of patients. I think that's where cancer biology has turned now—one disease is not defined by its histology; it's defined by its underlying molecular biology.” 40:29 – A message they'd like to share with children going through cancer treatment and with their parents and families

A new publication by six current and former American Cancer Society grantees describes the challenges faced by early-career investigators as a result of the pandemic and offers recommendations “to help institutions and individuals develop effective strategies to promote success and career advancement.” They joined the TheoryLab podcast to talk about key takeaways from their article, which “highlights the aftermath of the pandemic on work–life balance, promotion, tenure, funding, networking, and mentoring, and make recommendations that can help remediate these problems.” “Overstretched and overlooked: solving challenges faced by early-career investigators after the pandemic” was published in the journal Trends in Cancer: (https://www.cell.com/trends/cancer/fulltext/S2405-8033(21)00158-8) 3:41 – Brock Humphries, PhD, is a postdoctoral fellow at the University of Michigan. Priscilla Hwang, PhD, is an Assistant Professor in Biomedical Engineering at Virginia Commonwealth University. Aga Kendrick, PhD, is a postdoctoral fellow at University of California, San Diego Medical Center. Rajan Kulkarni, MD, PhD, is an Associate Professor of Dermatology at Oregon Health and Science University. Rachel Pozzar, PhD, is a nurse scientist at Dana-Farber Cancer Institute and Instructor of Medicine at Harvard Medical School. Rebeca San Martin, PhD, is a postdoctoral fellow at the University of Tennessee, Knoxville. 5:10 – What does it mean to be an “early-stage cancer researcher?” 9:56 – The unique challenges faced by early-career scientists 15:01 – How the American Cancer Society encouraged a conversation about how to surmount these challenges 16:33 – Some of the most striking things they learned from each other 22:47 – Productivity issues faced by early-stage researchers 24:19 – How cancer research labs have functioned during the pandemic 29:35 – How the pandemic has impacted the tenure clock for clinician scientists 34:21 – Ways to promote mental health among early-career investigators 37:36 – Some concluding thoughts about improving the environment for early-stage cancer researchers 40:26 – Their message for cancer patients, survivors, and caregivers

Two American Cancer Society grantees—one with a recent publication on the early mechanisms of lung cancer initiation, the other with a new study out on the development of melanoma resistance during the earliest phases of treatment—joined the podcast for a conversation about catching the problem early. This conversation is geared for a scientific audience, until the last few minutes. Sabrina Spencer, PhD, is Associate Professor of Biochemistry at University of Colorado, Boulder. She recently published a study in Nature Communications on “Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signaling:” https://www.nature.com/articles/s41467-021-21549-x?elqTrackId=2842c2f36cc243139afc4151f4f48ee6. Xaralabos (Bob) Varelas, PhD, is Associate Professor of Biochemistry at Boston University School of Medicine. He recently published work in Proceedings of the National Academy of Sciences of the United States of America titled, “Aberrant epithelial polarity cues drive the development of precancerous airway lesions:” https://www.pnas.org/content/118/18/e2019282118. 1:08 – Dr. Varelas on his recent study, which offered insights into mechanisms that drive the onset of lung squamous cell carcinomas 4:20 – Dr. Spencer asks clarifying questions about how they disrupted the polarity… 5:08 – …and whether the Crumbs3 mutation occurs in patients or was a way to initiate the system 7:56 – A provocative question from Dr. Spencer: “would that mean that a precancerous lesion would be a candidate for treatment with some of these clinically approved drugs?” 9:25 – “Can you connect increased ERBB signaling to actual increased cell cycling?” 10:48 – Dr. Spencer talks about her interest in the origin of drug resistance in cancer and her recent paper, which focused on melanoma 20:15 – Dr. Varelas asks how broadly applicable these findings are to other cancers 22:10 – “Why do you think some of the cells escape? Is there an underlying difference in the cells to begin with? Or are some cells randomly taking on some kind of adaptive mechanism?” 28:11 – The impact of American Cancer Society funding on their research

When tumors grow within the body they press on surrounding tissues, building up pressure. Pancreatic cancer builds up more pressure than any other cancer. Why is that? How do cancer cells adapt to this high-pressure environment or take advantage of it? In the words of Liam Holt, PhD, “Normal cells and early-stage cancer cells stop growing when pressure builds up. In contrast, in advanced cancer, compression can change cellular behavior to drive migration of cancer cells to other organs or confer resistance to chemotherapy… By determining the fundamental biology of pressure adaptation, we may discover strategies to treat this currently untreatable disease.” Liam Holt, PhD, is Associate Professor at the NYU School of Medicine. 1:50 – Why do pressure and compression matter for normal cells? “From the earliest embryo through to astronauts, we can find really good examples of how cells are responding to their mechanical environment to make sure they do just the right thing.” 6:09 – What happens when a tumor starts to grow? How does that affect nearby normal cells? 11:08 – Why there is so much compressive stress inside pancreatic tumors 16:24 – If we gain a better understanding of how pressure impacts pancreatic cancer, could that help us prevent or treat cancer? 22:13 – How a high-pressure environment drives the diversity of cancer cells 26:19 – “You can usually tell if it's a good idea because it seems super obvious” 29:06 – On an educational outreach initiative he co-founded called Science Sketches https://www.sciencesketches.org/ 33:48 – The impact American Cancer Society funding has had on his research 34:59 – A message he'd like to share with cancer patients, survivors, and caregivers

In this episode, Gustavo Martinez, PhD, and Daniel Herranz, PhD, discussed their new cancer research publications. Dr. Martinez talked about his research into how T cells respond in the context of cancer, and Dr. Herrera explained his lab's findings related to targeting cancer metabolism in leukemia. Gustavo Martinez, PhD, is Assistant Professor at Rosalind Franklin University. He received American Cancer Society funding to support his research into T cell exhaustion and boosting our immune system's response against cancer. Daniel Herranz, PhD, is Assistant Professor of Pharmacology at Rutgers, The State University of New Jersey. His ACS-funded research focuses on T-cell acute lymphoblastic leukemia. The first half of the conversation is more technical and is directed towards a scientific audience. The second part, starting at 17:27, is for all audiences. 1:38 – Dr. Martinez on the focus of his lab and takeaways from his recent publication in The Journal of Immunology titled, “Kdm6b Regulates the Generation of Effector CD8+ T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes:” https://www.jimmunol.org/content/early/2021/04/16/jimmunol.2001459 4:40 – What are some next steps? Are there downstream targets that could be activated? 7:54 – Dr. Herranz talks about why he's interested in targeting cancer metabolism in leukemia and shares findings published in his recent paper in Blood, “A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia:” https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020008955/475782/A-novel-and-highly-effective-mitochondrial 12:00 – Dr. Martinez asks about his thoughts regarding combination therapy 14:49 – Differences in immune response in younger patients 17:27 – Dr. Herranz provides a nice explanation of how his lab couples basic biology with a therapeutic approach 18:35 – Dr. Martinez explains his lab's focus on modulating our own immune system's response against the tumor cells 19:44 – They discuss the impact of ACS funding on their research and careers 23:07 – On improving diversity in cancer research and introducing younger students to science

In this episode, Ran Li, PhD, and Daniel Heller, PhD, discuss new advances in using nanoparticles to deliver drugs to cancer cells. Dr. Li was recently the first author of a paper in Nature Nanotech that described how cancer cells could be tricked into thinking they're starved for nutrients, causing them to increase consumption of a cancer drug attached to the protein, albumin. Dr. Heller published a review earlier this year that “highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs and, consequently, clinical outcomes.” Ran Li, PhD, is an American Cancer Society – Ellison Foundation Postdoctoral Fellow and Instructor at Massachusetts General Hospital and Harvard Medical School. Daniel Heller, PhD, is Associate Member at Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center. He is a two-time American Cancer Society grantee, having received a Postdoctoral Fellowship and Research Scholar Grant. 0:58 – Dr. Li describes new findings published in Nature Nanotech, “Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer:” https://www.nature.com/articles/s41565-021-00897-1 3:12 – Dr. Heller notes that “I'm a big fan of this paper and had my lab do a journal club on this,” and explains what he found exciting about it 5:46 –KRAS mutant cells are “ravenously thirsty,” making them susceptible to the approach taken by Dr. Li: “By tricking the cancer cells into thinking that they've been starved, they do more macropinocytosis, thereby taking more albumin-bound drug” 9:32 – “Do you think this could change how people use and prescribe this drug?” 11:50 – Dr. Heller shares some of the challenges and opportunities associated with nanoparticle drug delivery outlined in his review from earlier this year on targeted drug delivery strategies for precision medicines 16:34 – Dr. Li reacts… 18:29 – …and then asks, “What do you think a major hurdle is to bringing these novel drug delivery materials and technologies into the clinic?” 21:49 – On improvements that need to be made to nanomaterials in order to enhance precision medicine

In this episode, two American Cancer Society grantees discuss recent findings related to how breast cancer patients feel about de-escalating chemotherapy as well as a new paper on comorbidities in breast cancer patients. The first half of the conversation is not necessarily technical, but it's geared for a scientific audience. The second half is a more general discussion for a lay audience. Avonne Connor, PhD, is a breast cancer epidemiologist focused on health disparities research. She is Assistant Professor of Epidemiology and Oncology at the Bloomberg School of Public Health and has a joint appointment at the Sidney Kimmel Comprehensive Cancer Center. She recently published findings in the journal Cancer on “Comorbidities and the risk of cardiovascular disease mortality among racially diverse patients with breast cancer:” https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33530 Gabrielle Rocque, MD, is a breast medical oncologist and health services researcher with an interest in quality and value in health care delivery. She is an Associate Professor of Medicine at The University of Alabama at Birmingham with joint appointments in hematology and oncology as well as gerontology, geriatrics, and palliative care. Her recent paper in Cancer Medicine was on “Patient perspectives on chemotherapy de‐escalation in breast cancer:” https://onlinelibrary.wiley.com/doi/10.1002/cam4.3891 3:02 – Dr. Rocque shares takeaways from her recent study on patients' “interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation” 8:44 – How the pandemic influenced patients' decisions 10:58 – How she became interested in exploring patient perspectives on de-escalating treatment 12:44 – Dr. Connor discusses findings on “associations between newly diagnosed comorbidities and the risk of cardiovascular disease mortality among (breast cancer) patients” 20:36 – Dr. Rocque reacts to the paper and asks, “Where do we go from here in terms of interventions?” 24:40 – On how a cancer diagnosis can prompt patients to reflect on their lives and how they can take care of their health 27:55 – Dr. Connor talks about how rewarding and exciting it is to train a postdoctoral fellow 29:39 – Dr. Rocque on her passion – how do we provide the best supportive care to patients, and how do we integrate research and clinical care? 30:50 – How American Cancer Society funding impacted their research and careers

Finding out that a loved one has cancer can bring many changes. Doctors and nurses receive years of training in patient care, but family caregivers are often thrust into this role overnight with no training on the critical processes that their loved ones depend on them to do properly every day. Rachel Cannady—as Strategic Director of Cancer Caregiver Support at the American Cancer Society—creates resources that empower caregivers with the resources and information they need. Visit https://cancer.org/caregivers to learn more about what to expect if you become a caregiver for a person with cancer, and get tips for making sure that you take care of yourself as well. Among the resources there are the Interactive Caregiver Resource Guide and the Caregiver Support Video Series. The Interactive Caregiver Resource Guide is a comprehensive tool to help you learn how to care for yourself as a caregiver, better understand what your loved one is going through, and develop skills for coping and caring. It can be accessed or downloaded here: https://www.cancer.org/content/dam/cancer-org/cancer-control/en/booklets-flyers/american-cancer-society-caregiver-resource-guide.pdf The Caregiver Support Video Series provides educational support to caregivers as they assist with the everyday needs of cancer patients and provide self-care techniques to improve their quality of life. Short videos provide guidance related to, for example, drain care, managing side effects, and managing medication. It's available at https://www.cancer.org/treatment/caregivers/caregiver-support-videos.html. 2:20 – Creating evidence-informed resources for cancer caregivers 4:12 – On the village of cancer care in the United States 6:27 – “The bigger the village, the better the help” Some of the many responsibilities of cancer caregivers—information seeking, emotional support, decision making, navigating financial concerns, etc. 9:53 – On findings from the National Quality of Life Survey for Caregivers, a study that followed a group of caregivers over eight years 16:01 – “Nearly 50% of the caregivers at post-diagnosis said that they need help helping their loved one deal with the emotional stress of cancer.” 17:30 – There's also a positive benefit from providing care – caregiving can create meaning in people's lives 20:33 – The Caregiver Resource Guide, the Caregiver Support Video Series, and other resources developed through the American Cancer Society's Caregiver Support Program https://www.cancer.org/treatment/caregivers.html 29:16 – How these resources can empower caregivers and help them feel more confident, prepared, and at ease 31:20 – On the impact of COVID-19 on cancer caregiving

Elyse Park, PhD, is Professor of Psychiatry at Harvard Medical School, Director of the Health Promotion and Resiliency Research Program at Massachusetts General Hospital (MGH), Associate Director of Survivorship Research, and Psychosocial Services for the MGH Cancer Center Survivorship Program. Her most recent American Cancer Society grant focuses on developing a health insurance navigation program for childhood survivors. Travis Baggett, MD, MPH, is Associate Professor of Medicine at Harvard Medical School, Director of research at Boston Health Care for the Homeless Program, and an MGH research scholar. His ACS grant supports research into lung cancer screening navigation for homeless people. Sanja Percac-Lima, MD, is Associate Professor of Medicine at Harvard Medical School, a primary care physician at the MGH Chelsea Community Health Care Center, and physician leader for cancer outreach at MGH Cancer Center. A former ACS grantee, her research focuses on cancer prevention in ethnic and racial minorities. 5:42 – Dr. Park on her research into lung cancer screening, helping smokers quit, and helping survivors cope with stress and enhance their resiliency 8:46 – Dr. Percac-Lima on her research into alleviating disparities in cancer care and screening in vulnerable populations 11:39 – Dr. Baggett on a patient navigation program to help current and former homeless individuals to quit smoking and get lung cancer screening 14:32 –Taking behavioral interventions to the next level 17:14 –Reducing colorectal cancer screening disparities through patient navigation 22:09 –The encouraging progress there has been in the recognition of health equity issues 29:05 – Dr. Park on helping cancer survivors to improve their access and use of health insurance 33:38 – On the benefits of patient navigation during the COVID-19 pandemic 38:09 – On social justice and the work of the homelessness housing and health lab 41:41 – Why Massachusetts General Hospital is such a wonderful research environment 48:32 – The impact of ACS funding on their research 53:05 – A message for cancer patients, survivors, and caregivers

In this episode—which is for a scientific audience until the 27-minute mark—a current American Cancer Society grantee and a former grantee spoke with each other about their recently published new findings in cancer research. Alessandro Gardini, PhD, an Assistant Professor at The Wistar Institute, studies the epigenetic control of transcription during cell differentiation and oncogenesis. He recently published work in Cell titled “The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer:” https://pubmed.ncbi.nlm.nih.gov/34004147/. Yuan He, PhD, is Assistant Professor (but just received word that he's being promoted to Associate Professor!!) at Northwestern University. The He lab The He lab uses cryo-electron microscopy (cryo-EM) and other biophysical and biochemical approaches to understand “the molecular mechanisms by which large, multi-subunit complexes engage in DNA-centric processes.” Dr. He recently published findings in Science on, “Structure of the human Mediator-bound transcription preinitiation complex:” https://science.sciencemag.org/content/372/6537/52. 4:12 – Dr. Gardini describes his new paper: “what we found is that when you combine CDK9 inhibition with activation by small molecules of the PP2A phosphatase…we get a much better block on transcription in these tumors…” 9:10 – Interesting question from Dr. He on the mysterious integrator complex 11:11 – “What do you think about this tug of war of the phosphatase competing with CDKs…?” 14:19 – Dr. He shared takeaways from his new paper: “And this eventually allowed us to build a model of how this gigantic 57-sub-unit machinery recognized CTD from the polymerase…” 19:11 – Dr. Gardini professes his love for CTD 20:39 – “What do you think is the threshold of phosphorylation in order for the mediator to start losing affinity…?” 25:36 – “Could we possibly think that both mediator and integrator are actually bound to non-phosphorylated CTD at the same time or could there actually be competition…?” 27:46 – Why is this work important? Why should a cancer patient, survivor, or caregiver be excited about these publications?

Lisa McKenzie, PhD, has a new American Cancer Society research grant to explore the relationships between oil and gas environmental exposures and childhood acute lymphoblastic leukemia (ALL). The award builds upon her preliminary studies, which suggested that children living near oil and gas wells “may be economically disadvantaged and at greater risk for childhood leukemia.” According to Dr. McKenzie—who is a Clinical Assistant Professor at the University of Colorado's School of Public Health—approximately 3 million children in the United States live within one mile of an oil and gas well. In this episode, Dr. McKenzie explains how she plans to evaluate the association between exposures from oil and gas development and childhood leukemia risk and why this work is critically needed to support state and federal policy. 4:51 – Lisa McKenzie, PhD, Clinical Assistant Professor at the University of Colorado's School of Public Health 6:11 – On fracking and how oil and gas are removed from the ground 8:38 – How tapping into unconventional resources such as shale has brought the oil and gas industry into more communities 11:12 – On concerns that communities have raised about oil and gas environmental exposures 13:49 – What we know about carcinogens associated with the oil and gas industry 15:57 – On childhood acute lymphoblastic leukemia (ALL) 18:19 – Why it's particularly concerning for children to be exposed to carcinogens 23:38 – Has proximity to oil and gas activity been associated with childhood ALL? 25:10 – How many children in the United States live near such activity? 26:07 – How she plans to build on her preliminary data using American Cancer Society funding 28:35 – Why she hopes her research could make a difference for parents and children 32:13 – On the state, national, and global policies for oil and gas environmental practices 34:07 – How ACS funding will allow her to continue her research 35:46 – A message she'd like to share with cancer patients, survivors, and caregivers

In this episode—which skews more toward a scientific audience until the last five minutes—two American Cancer Society grantees spoke with each other about their recently published new findings in breast cancer research. Sonia de Assis, PhD, is interested in epigenetic inheritance: “In addition to genetic material or DNA, our parents also pass to us molecular memory of their environmental exposures, and that can affect our risk or predisposition to disease including cancer.” Matthew Sikora, PhD, focuses on invasive lobular carcinoma, a type of invasive breast cancer. He feels that “advances in treatment are hindered by our poor understanding of the distinct biology of invasive lobular carcinoma,” and his lab has identified a potential therapeutic target. Sonia de Assis, PhD, is an Assistant Professor of Oncology at Georgetown University. She recently published findings showing that, “systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation:” https://www.nature.com/articles/s41598-021-86548-w. Matthew Sikora, PhD, of the Univ. of Colorado Denver, Anschutz Medical Campus and DC, is an Assistant Professor of Pathology. His latest work is titled, “Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive lobular carcinoma of the breast:” https://pubmed.ncbi.nlm.nih.gov/33947745/. 1:49 – Dr. de Assis on epigenetic inheritance and her recently published findings 5:30 – Reactions from Dr. Sikora and what stood out to him about Dr. de Assis's findings: “Figure 2A really smacked me in the face and just got me going…” 9:23 – “Do you think it's actually the tRNA levels that are different that are causing the phenotype, or are those indicative of a different epigenetic context in the sperm?” 11:31 – “One thing I want to make clear is that we think the non-coding RNAs act with a hit-and-run effect…” 12:35 – Dr. Sikora on invasive lobular carcinoma and his new publication 16:08 – Invasive lobular carcinoma versus invasive ductal carcinoma 19:12 – “That's a fabulous question, and my R01 reviewers had the exact same question a few cycles ago…” 22:27 – “How do you see using MDC1 as a therapeutic target because of this dichotomy that's a tumor suppressor but also an oncogene?” 24:30 – They note some interesting connections between their work 27:13 – Dr. de Assis explains why it's important to understand epigenetic memory 28:50 – Dr. Sikora describes why he became interested in invasive lobular carcinoma

In this episode, three researchers from Dartmouth who are investigating very different aspects of cancer joined the podcast to share their work. One of the guests, James Moseley, PhD, summed up why a diversity of scientific approaches and collaboration among researchers is so important: “We're all in this together. There are so many different angles to fighting cancer, whether it be here at Dartmouth—where we've got folks working on the level of cells and proteins all the way up through patient care and beyond—or through the ACS. This is really a team effort, and we're all kind of working on our individual parts, but (this is) a reminder that we're all working together to tackle all these different aspects of cancer with the ultimate goal of helping patients and survivors.” Amber Barnato, MD, MPH, MS, is the Susan J. and Richard M. Levy 1960 Distinguished Professor in Health Care Delivery. Her research focuses on variation in end-of-life intensive care unit and life-sustaining treatment use. Kathleen Lyons, ScD, is Associate Professor of Psychiatry. Here research focuses on cancer rehabilitation and palliative and supportive care. James Moseley, PhD, is Professor of Biochemistry and Cell Biology. His lab studies how cells coordinate cell growth and division. 5:10 – Dr. Barnato on making sure that end-of-life care aligns with personal goals, helps manage symptoms and emotional distress, and supports families 7:08 – Dr. Lyons on how rehabilitation science helps with symptom management and side effects from cancer treatment 9:24 – Dr. Moseley on a different kind of decision making – how a cell decides that it's going to divide 13:02 – How early engagement of palliative care in cancer care improves quality of life and symptom management and can help extend life 16:02 – On the growing understanding of why “prehabilitation” before treatment is so important 20:24 – What we've learned from technological breakthroughs that have allowed researchers to watch individual proteins in cells 27:20 – Dr. Barnato's focus on medical decision making and patient-provider relationships 29:42 – How Dr. Lyons is focused on accelerating recovery from treatment and helping patients get back to doing the activities they want to do 35:30 – Dr. Moseley poses an interesting question: How does a cell know what size it is? 39:10 – On the collaborative, supportive environment at Dartmouth 40:49 – The impact of ACS funding on their research 49:55 – A message they'd like to share with cancer patients, caregivers, and survivors

To understand how cancer develops and spreads, and to develop better therapies, it’s critical to understand the tumor microenvironment, the immediate area around a tumor that “helps generate a supportive niche for it to develop and grow.” Johanna Joyce, PhD, joined the podcast to explain that the diverse normal cells around a tumor are enmeshed with cancer cells. They’re integrated. They communicate and influence each other’s functions. Her lab’s goal is “to try and either block this cellular conversation or redirect it towards a more constructive dialogue that helps fight the tumor and not support it.” Johanna Joyce, PhD, is Professor at the University of Lausanne and Full Member of the Ludwig Institute for Cancer Research. 4:32 – What is the tumor microenvironment? 6:00 – Why it’s similar to the immense complexity of a forest’s ecosystem 8:19 – Do tumors somehow create or remodel their microenvironments? 12:42 – “The tumor microenvironment can have a major impact on how a given cancer responds to therapy in a number of different ways…” 18:23 – On the unique aspects of the tumor microenvironment in the brain 22:02 – On her fantastic new study showing that different brain cancers have different microenvironments based on whether the tumors started in the brain or spread to the brain 28:15 – Surprising findings from that study – the immense complexity and diversity of immune cells in the tumor microenvironment 32:12 – How can we translate these findings to the clinic? 36:22 – Why it’s so important to understand how different lifestyles, diets, levels of activity, and environmental exposures impact patients’ tumor microenvironments 38:20 – The impact that American Cancer Society funding had on her career 40:41 – Her message for cancer patients, survivors, and caregivers

When Delaram Cavey was diagnosed with stage IV lung cancer seven years ago, she was fortunate to have two wonderful daughters to help her along her journey. Delaram and her older daughter, Catherine Cavey, joined the podcast to share the story of Delaram’s cancer diagnosis and treatment. They also talked about how the cancer experience has sparked an interest in science in their family. Catherine has created an educational resource to raise awareness of epidermal growth factor receptor (EGFR) mutations, and they’ve founded GoMENA to create pathways for immigrant girls of Middle Eastern and North African descent to become engineers in the United States (https://gomena.us/). Delaram Cavey is a career member of the United States foreign service. Her daughter, Catherine Cavey, is in the 10th grade at Edison High School in Fairfax, Virginia. 5:09 – The story of Delaram’s lung cancer diagnosis 9:08 – Catherine on her memories of her mom’s diagnosis 12:54 – What it was like for Delaram, as a never smoker, to learn she has lung cancer 13:46 – How the cancer journey brought their family closer together 17:05 – How Catherine has helped raise awareness of epidermal growth factor receptor (EGFR) mutations 20:40 – How her mom’s experience has impacted Catherine’s career goals 23:42 – On living your best life, every day 28:46 – Advice from Catherine for other children whose parents are diagnosed with cancer 29:36 – Why they founded GoMENA to create pathways for immigrant girls of Middle Eastern and North African descent to become engineers in the United States https://gomena.us/

Melanoma is much less common than some other types of skin cancers, but it is more dangerous because it’s much more likely to spread to other parts of the body if not caught and treated early. While there have been some exciting advances in melanoma research in recent years, there is much left to learn about, for example, how it spreads, how it resists treatment, and therapies could be improved. In this episode, three scientists at the Sidney Kimmel Cancer Center who are investigating different aspects of melanoma explain why it’s a challenging disease, describe recent advances against it, and underscore why there are so many reasons to be excited. 4:11 - Andrew Aplin, PhD, is Associate Director of Basic Research at the Sidney Kimmel Cancer Center and Professor in the Department of Cancer Biology. Chris Snyder, PhD, is Associate Professor in the Department of Microbiology and Immunology at the Sidney Kimmel Cancer Center. Neda Nikbakht, MD, PhD, is Assistant Professor in the Department of Dermatology and Cutaneous Biology at the Sidney Kimmel Cancer Center. 4:42 – Dr. Aplin on his research into why melanoma is so resistant to therapy 5:59 – Dr. Snyder on his work into why the immune system sometimes doesn’t seem to recognize cancer 8:11 – Dr. Nikbakht, a dermatologist who sees patients with skin cancer, discusses how she studies the skin microbiome to learn what properties promote melanoma 10:43 – The tremendous recent advances in melanoma treatment 13:59 – What we’ve learned about the immune system in recent years 18:02 – A physician’s perspective on recent advances in melanoma research 22:04 – The big picture goal of Dr. Aplin’s research 26:51 – Dr. Snyder’s move into cancer immunology 32:00 – Dr. Nikbakht on the tremendous importance of patient samples in research 37:46 – How the collaborative environment at the Sidney Kimmel Cancer Center enhances their research 43:26 – The impact of ACS funding on their work 47:16 – Why advances made during the push to develop COVID-19 vaccines could be very impactful for cancer research 49:01 – A message they’d like to share with cancer patients, survivors, and caregivers

Lung cancer is the leading cause of death from cancer, but if it’s found at an earlier stage, when it is small and before it has spread, it is more likely to be successfully treated. To take us through the state of lung cancer screening in the US—big picture issues, challenges faced by patients and clinicians, and reasons for excitement—we were joined by two leading experts in the field. Christopher Slatore, MD, MS, is an investigator for the Portland VA Health Service Research and Development Center of Innovation, Center to Improve Veteran Involvement in Care (CIVIC). He’s Associate Professor of Medicine at Oregon Health & Science University, and he’s a pulmonologist who conducts lung cancer screening. He’s also an American Cancer Society Research Scholar Grant recipient. Anne Melzer, MD, MS, is Assistant Professor of Medicine at the University of Minnesota Medical School. She is an Investigator at the Minneapolis VA Center for Care Delivery and Outcomes Research. And she is a pulmonologist who is the medical director of the lung cancer screening at the Minneapolis VA. The American Cancer Society recommends annual lung cancer screening with a low-dose CT scan for certain people at higher risk for lung cancer. Visit cancer.org for details: https://www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/lung-cancer-screening-guidelines.html 4:18 – Welcome Dr. Melzer and Dr. Slatore 5:51 – Dr. Melzer on the lung cancer burden in the United States 8:46 – Dr. Slatore on the state of lung cancer screening in the US 12:08 – Some of the big picture problems they’re trying to solve related to lung cancer screening 16:47 – The US Preventive Services Task Force’s recent recommendation regarding lung cancer screening: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening 23:01 – Challenges that exist for patients when it comes to lung cancer screening 25:28 – Some of the frustrations clinicians have with lung cancer screening 30:39 – “We need to make it easier for patients and primary care providers to do lung cancer screening.” 34:57 – It all comes down to an old Seinfeld episode: https://www.youtube.com/watch?v=4T2GmGSNvaM 36:31 – The impact of ACS funding on Dr. Slatore’s research 37:28 – The aspect of her research that Dr. Melzer is most excited about 38:50 – Messages they’d like to share with cancer patients, survivors, and caregivers

The American Cancer Society is committed to maintaining a broad cancer research portfolio—any type of cancer, within any part of the cancer research continuum. This episode is a perfect example of this commitment and features three cancer researchers from the UPMC Hillman Cancer Center. Kathy Shair, PhD, studies how the Epstein-Barr virus causes cancer. Sarah Hengel, PhD, is investigating why unrepaired DNA leads to cancer. And Yuri Bunimovich, MD, PhD, conducts research into the role of our body’s nerves in melanoma growth. 1:47 – Yuri Bunimovich, MD, PhD, is Assistant Professor in the Department of Dermatology and member of the Cancer Immunology and Immunotherapy program at Hillman Cancer Center Sarah Hengel, PhD, is an American Cancer Society postdoctoral fellow at the Hillman Cancer Center in the Department of Pharmacology and Chemical Biology in the Kara Bernstein lab. Kathy Shair, PhD, is Assistant Professor of Microbiology and Molecular Genetics and an investigator in the Cancer Virology program at the Hillman Cancer Center 3:11 – Dr. Shair on how her lab is focused on understanding how chronic infections can turn bad and result in cancer 4:13 – Dr. Hengel’s research into a subset of breast and ovarian cancers 6:17 – Dr. Bunimovich on the role of nerves in the tumor microenvironment in melanoma and other cancers 12:13 – Dr. Shair on recent advancements that help us understand the circumstances under which the Epstein-Barr virus can lead to cancer 22:24 – Dr. Hengel explains how our improved understanding of different mutations is leading to more personalized therapies 26:38 – Dr. Bunimovich explains how melanoma can injure nerves, creating an immune-suppressive environment that protects the melanoma from the body’s immune response. 35:16 – Dr. Shair on how Epstein-Barr viruses’ interference with DNA repair can be used to our advantage 38:00 – Dr. Hengel on how gathering more information about these mutations is critical to developing novel therapeutic targets 40:29 – The three aspects of his research Dr. Bunimovich is most excited about 45:28 – Dr. Shair and Dr. Hengel talk DNA repair and studying cancer in model organisms 47:21 – Dr. Bunimovich and Shair on viruses and cancers 51:42 – The impact of ACS funding 53:45 – A message for cancer patients, survivors, and caregivers

At first glance, the work of Eva Hernando and Thales Papagiannakopoulos might not seem to have much in common. Dr. Hernando studies the contributions of non-genetic alterations to the aggressive behavior of melanoma. Dr. Papagiannakopoulos is applying CRISPR/Cas9 to study lung cancer. But in this conversation, Drs. Hernando and Papagiannakopoulos take us through the ins and outs of their research into why cancer grows and spreads, and we learn how they learn from each other, how NYU Grossman School of Medicine encourages collaboration, and why new directions in cancer research have them feeling optimistic. 3:05 – Eva Hernando, PhD, is Professor in the Department of Pathology and Assistant Dean for Research at the NYU Grossman School of Medicine. Thales Papagiannakopoulos, PhD, is Associate Professor in the Department of Pathology at NYU Grossman School of Medicine. 5:26 – Dr. Hernando on why cancer cells metastasize 10:10 – Why she studies metastasis in melanoma 13:28 – Dr. Papagiannakopoulos on why it’s so hard to understand what the cancer genome is telling us 20:50 – Dr. Papagiannakopoulos on why he studies lung cancer 23:32 – Dr. Hernando on the biggest challenge she’s facing as a melanoma researcher 27:42 – Dr. Papagiannakopoulos on new directions in lung cancer research 30:34 – On encouraging research collaborations at NYU 35:16 – How ACS funding has impacted their cancer research

Pancreatic cancer is a terrible disease. “The 5-year relative survival rate for all stages combined is 10%,” according to Cancer Facts & Figures 2021. “Even for the small percentage (11%) of people diagnosed with local disease, the 5-year survival rate is only 39%.*” But cancer researchers are learning more every day about how to find pancreatic cancer early and develop targeted therapies. Laura D. Wood, MD, PhD, a clinician scientist at Johns Hopkins University School of Medicine, joined the podcast to explain why pancreatic cancer is difficult to detect early and how her team is approaching the problem. 2:34 – Laura D. Wood, MD, PhD is an Associate Professor in the Department of Pathology and Director of GI Pathology in the Division of Gastrointestinal and Liver Pathology at the Johns Hopkins University School of Medicine. And she’s an American Cancer Society Research Scholar. 3:32 – As a graduate student she was among the first in the world to sequence the whole exomes of human tumors. What are whole exomes? 5:38 – Why this accomplishment was important and how much technology has advanced since then 9:03 – How a more complete picture of the cancer genome changes our understanding of that cancer 13:37 – Why early detection of pancreatic cancer is such a clinical challenge 17:13 – “It’s actually on course to be the 2nd-leadest cause of cancer death within a few years” 21:15 – What she’s learned from genetics about the development of precancerous lesions in the pancreas 24:56 – How it’s different from colorectal cancer screening 26:37 – How can we tell which lesions are going to turn into cancer? 29:36 – On growing mini-tumors in fancy science jello to understand cancer cell invasion 31:37 – How she is studying pancreatic cancer from both ends of the spectrum 33:01 – How her clinical training and knowledge of genetics and morphology helps her think about what research questions matter to cancer patients 34:56 – Progress she hopes to see in the pancreatic cancer research field in the next 5 years 36:54 – A message she’d like to share with cancer patients, survivors, and caregivers *Source: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf

How can we use the exceptional greed of cancer cells against them? They gobble up all the resources in their local environment, spread to another area, and then gobble up more resources. Thales Papagiannakopoulos, PhD, explains that there’s a cost to that. A cancer cell takes a lot of fuel, but it produces a lot of waste. It has a few tricks for getting rid of that waste, such as taking advantage of antioxidants in our diet, but Dr. Papagiannakopoulos and his team are exploring some innovative approaches to this problem. In this conversation, Dr. Papagiannakopoulos takes us through cancer metabolism and the implications of ACS-funded cancer research that has moved into clinical trials. 3:30 - Thales Papagiannakopoulos, PhD, is Associate Professor in the Department of Pathology at NYU Grossman School of Medicine 4:26 –What does metabolism do for normal cells? How does the metabolism of immune cells help them fight off infections? 9:03 – How does a cell’s need for energy change as it becomes a cancer cell? 11:06 – Cancer cells as factories 15:02 – How a higher metabolism can also damage cancer cells… 17:01 – How cancer cells accumulate and clear out free radicals 23:50 – How cancer cells take advantage of antioxidants in our diet 26:44 – Exciting therapeutic implications resulting from these insights 32:17 – How ACS funding helped move his research into clinical trials

A key challenge in treating some cancers is the ability to distinguish tumors that are likely to metastasize from indolent disease that can be managed with active surveillance. Dr. Peder Larson has developed a non-invasive imaging method based on magnetic resonance imaging (MRI) to measure the rate at which a tumor creates lactic acid and transports it out of cells. In this conversation he explains how the technology works and how he hopes to create imaging biomarkers to identify cancers that require aggressive therapy. 3:13 – Peder Larson, PhD, is an Associate Professor in Residence and a Principal Investigator in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. He’s also a core member of the joint UC Berkeley–UCSF Graduate Program in Bioengineering. 4:13 – How oncologists use imaging data 8:57 – How does MRI work? 13:11 – How MRIs are used in treatment decisions… 15:56 – …and some of their limitations 17:44 – How we could use MRIs to understand cancer metabolism 21:55 – On the special type of MRI focused on differences in metabolism, called Hyperpolarized carbon-13 magnetic resonance imaging, how it works, and why it’s so cool 25:43 – How he’s improved this technology 28:57 – The impact of ACS funding on cancer research 31:25 – A message he’d like to share with cancer patients, survivors and caregivers

Screening can prevent colorectal cancer through the detection and removal of precancerous growths (polyps), as well as detect cancer at an early stage, when treatment is usually less intensive and more successful. People living in rural areas are much less likely to undergo screening due to a number of barriers, but some rural clinics have achieved high colorectal cancer screening rates despite such constraints. Dr. Jennifer Weiss of the University of Wisconsin-Madison joins the podcast to talk about how these clinics have been successful in “developing relevant, impactful, and sustainable approaches to increasing colorectal cancer screening in rural communities.” The American Cancer Society recommends regular colorectal cancer screening for people at average risk starting at age 45: https://www.cancer.org/healthy/find-cancer-early/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html. 4:45 – Jennifer Weiss, MD, MS is Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at the University of Wisconsin-Madison. She’s a two-time American Cancer Society grantee. 5:21 – Why she has described colorectal cancer as the “most preventable, but least prevented cancer” 8:15 – The American Cancer Society recommends regular colorectal cancer screening for people at average risk starting at age 45 13:19 – On why where you live can impact access to colorectal cancer screening 16:23 – Some rural clinics are doing better than others in terms of colorectal cancer screening and outcomes… 20:11 – …why is that? What are they doing right? 22:58 – A great real-life example of a rural clinic boosting screening rates 29:05 – Gaps that she hopes her research will fill 30:23 – What she’s most excited about 33:18 – A message she’d like to share with cancer patients, survivors and caregivers

Dr. Nicole Steinmetz is well on her way in her mission to “push new frontiers in medicine and bio-nanotechnology through the design, development and testing of materials and biologics derived from plant viruses.” Plant viruses? Plant viruses. They’re non-infectious to humans. When injected into a tumor the immune system is alerted to their presence; finding no threat from the plant virus the immune cells fight the tumor instead. Dr. Steinmetz talks us through the technology she’s developed, explains how it can advance immunotherapy, and gives us a glimpse of how she and her team are applying this platform toward COVID-19 vaccine development. 1:52 – Nicole Steinmetz, PhD, Professor of NanoEngineering and Director of the Center for Nano-ImmunoEngineering at the University of California, San Diego 2:34 – What are nanoparticles? Why are they useful in medicine? 7:11 – The Ballad of the Ferrari and the Geo Storm 9:25 - How nanoparticles are useful in cancer diagnostic and therapeutic approaches 14:36 – Using plant viruses as nanotechnology (“They’re also naturally expert at the delivery of cargo” such as cancer therapeutics.) 20:40 – How her lab is using plant virus-based nanotechnologies to improve immunotherapy delivery 27:08 – How plant viruses nicely synergize with checkpoint therapies 31:04 – How nanotechnology has been applied to COVID-19 vaccine development 33:04 – The role her lab has played in developing COVID-19 vaccine candidates using plant viruses “that we could ship at room temperature around the world to people’s homes…You don’t even need to see a doctor; you can apply it like a bandage to get the vaccine.” 35:05 – On how this is a platform technology that could be used against the next strain, the next mutant, the next virus 36:28 – How support from the American Cancer Society has impacted her research 38:06 – Her message for cancer patients, survivors and their caregivers Stick around until the end for a few bonus questions on Baldeneysee, surfing, whales, and her favorite teacher growing up

When it comes to how diet affects colorectal cancer risk, it’s not just a question of whether you eat your fruits and vegetables. Are you eating the right combinations of foods? How do your dietary patterns influence your metabolism? How does genetics play a role? Dr. Fred Tabung just received an American Cancer Society research grant to explore these questions. He talked about how his study will identify specific groups for which certain dietary patterns might play a significant role in increasing or decreasing colorectal cancer risk. Fred Tabung, PhD, MSPH, is Assistant Professor in the Department of Internal Medicine at The Ohio State University and the Division of Medical Oncology at the Ohio State University Comprehensive Cancer Center. 5:30 – Why the nutritional epidemiology of cancer is important 7:05 – On some current trends in colorectal cancer diagnosis and mortality 8:48 – Why he thinks the impact of our habitual dietary patterns on our metabolism and gut microbiome could impact colorectal cancer risk 11:53 – Why insulin could be important in the development of colorectal cancer 14:40 – Why it's important to look at food combinations 18:02 – On his new ACS-funded study that includes more than 700,00 men and women across four continents… 20:00 – …and how it could lead to exciting new opportunities to impact risk for colorectal cancer through changes to dietary patterns 24:07 – Some helpful advice about specific healthy food combinations 25:45 – A message he’d like to share with the donors who made his ACS research grant a reality

While working as program directors at Georgia Institute of Technology’s VentureLab—Georgia Tech’s incubator for technology startups—Melissa Heffner and Sara Henderson saw an opportunity to create a program for female entrepreneurs. Female Founders is “a four-week virtual cohort experience where participants gain a foundational knowledge of lean startup methodology and customer discovery while tackling topics associated with the specific journey of female-led startups:" https://www.icorpssouth.com/female-founders-initiative. Ms. Heffner joined the TheoryLab podcast along with three participants in the program to share advice for evidence-based entrepreneurship and talk about the exciting technology that is behind their respective start-ups. Melissa Heffner is a program director with Georgia Institute of Technology’s VentureLab and the co-creator of Female Founders. Ana Luz Quiroga Campano, PhD, is a postdoctoral fellow in the Biological Systems Engineering Laboratory at Emory University and Georgia Tech. She’s also the CEO of SANICKA. Allyson Jennings McKinney is a PhD candidate in the School of Electrical and Computer Engineering at the Georgia Institute of Technology. Kacie Kaile is a PhD candidate in Biomedical Engineering at Florida International University. 5:03 – On the purpose and goals of the Female Founders program 5:49 – Why they saw a clear need for a program specifically for female entrepreneurs 9:54 – Some of the ways they’re helping to set female entrepreneurs up for success 11:08 – Allyson Jennings McKinney on what attracted her to Female Founders 12:44 – On Solopulse—an exciting new technology she’s developed that utilizes a single pulse of a wave to create images of the surrounding environment—and its potential clinical impact 16:10 – Dr. Ana Luz Quiroga Campano on how the Female Founders program has met her needs as a postdoctoral fellow 18:21 – On the precision chemo-immunotherapy software tool developed by her company, SANICKA 21:45 – Kacie Kaile on how Female Founders has changed her entrepreneurial approach 23:37 – On a product she’s developed that provides a diagnostic assessment of tissue oxygenation using a smartphone with an add-on tool 28:43 – Dr. Quiroga on why scientists shouldn’t feel hesitant about becoming an entrepreneur when they have an idea 30:04 – Ms. McKinney with good advice on getting started as an entrepreneur 31:41 – Ms. Kaile on the benefits of starting a company with support from an academic institution 33:37 – Ms. Heffner with advice for cancer researchers thinking of starting a company in the oncology space

The troubling increase of early-onset colorectal cancer incidence and mortality has led to a shift in the age at which the American Cancer Society recommends beginning colorectal cancer screening, from age 50 to age 45. What are some of the biological and environmental factors that might be behind this rise in early-onset colorectal cancer? How can we prevent it? And what is behind the troubling racial and ethnic disparities we see in colorectal cancer incidence and mortality? Joining us to take us through these issues is one of the leading researchers in this space. Peter Campbell, PhD, is Scientific Director, Epidemiology Research, in the Population Science Department of the American Cancer Society. 4:05 – The main areas of focus in his research program 7:26 – The differing incidence and mortality rates for colorectal cancer in younger and older Americans 10:57 – On racial/ethnic colorectal cancer disparities 13:26 – Digging into the “why” behind some of these trends 19:36 – How the American Cancer Society is trying to reduce disparities and reverse the rise of early-onset colorectal cancer 23:04 – On the Colorectal Cancer Pooling Project 26:18 – Where his team hopes this work could lead in 5 years 28:37 – Thoughts on tumor heterogeneity (One of the challenges of colorectal cancer is that not only are tumors different from patient to patient, but they differ within individual patients as time progresses. Could these molecular differences in tumors could be associated with lifestyle? How could we find out?) 31:58 – On what it might mean for colorectal cancer survival if there are associations between how we live and colorectal cancer heterogeneity

The collaboration between Claudia Benavente, PhD, and Michael Emanuele, PhD, is a perfect example of how cancer researchers with overlapping interests but very different expertise can come together to find a new path forward in cancer research. They found each other through the American Cancer Society’s online community for current and former cancer research grantees. The Benavente Lab had previously identified a new protein with exciting therapeutic potential that is critical for tumor metastasis. Independently, the Emanuele Lab found that this protein is tightly controlled by a cellular machinery that functions to eliminate proteins within the cell. Together, they are collaborating on an ACS-funded research project to determine how this protein is made, how it functions, and how it’s eliminated, with the goal of creating novel target therapeutics for patients with triple-negative breast cancer. 2:55 – Claudia Benavente, PhD, is Assistant Professor of Pharmaceutical Sciences at the University of California, Irvine. Michael Emanuele, PhD, is Associate Professor in the Department of Pharmacology at the University of North Carolina at Chapel Hill and the UNC Cancer Center. 4:04 – What is triple-negative breast cancer? What does ‘triple negative’ mean? 7:48 – On a protein called UHRF1 that has therapeutic potential in other cancers with similarities to triple-negative breast cancer. What does UHRF1 do in normal cells? 10:50 – Why is it important in cancer cells? 13:45 – How Dr. Emanuele and Dr. Benavente struck up a collaboration through TheoryLab, the American Cancer Society’s online community for current and former research grantees 17:35 – “…maybe we could take advantage of the cell’s innate ability to get rid of UHRF1 and sort of trick it into shutting it off itself—not just shut it off, but get rid of it altogether…” 21:47 – How their complementary skill sets and expertise will help them figure out the best approach to target how UHRF1 is made, how it functions, and how it’s eliminated, with the goal of creating novel target therapeutics for patients with triple-negative breast cancer 25:41 – Steps they will take to determine the potential of therapeutically regulating UHRF1 removal in triple-negative breast cancer 28:54 – What most excites them about this project 32:46 – Keys to a productive scientific collaboration 34:56 – On the impact of ACS funding on their research 37:33 – A message they’d like to share with cancer patients, survivors, and caregivers

What does studying how cells communicate in round worms have to do with cancer in humans? In order for cancer cells to multiply indefinitely and metastasize to another part of the body, they have to communicate with each other. Understanding how they do that is critical to developing the next generation of cancer therapeutics. As American Cancer Society grantee Theadora Tolkin, PhD, puts it, “The signals that cancer cells use to communicate with one another are exactly the same signals that our healthy cells use every day to keep us alive and well. The difference between healthy communication and communication that leads to cancer, however, may have to do with the levels of signal sent or received. Sometimes, a cell becomes a cancer cell because it stops listening to the cells around it. Other times, cancer gets started when a cell thinks it hears a signal that’s not there.” In this conversation, Dr. Tolkin helps us understand the signal that she’s studying, called Notch, and how problems with Notch signaling can lead to cancer in different ways. Theadora Tolkin, PhD, is a postdoctoral fellow at NYU Langone Health in the Skirball Institute of Biomolecular Medicine, in the lab of Jane Hubbard, PhD. 5:02 – Just a fantastic story about her unusual road to a career in science 10:42 – Why C. elegans, a round worm, is such a useful model system for understanding cancer 12:56 – Why it is particularly important to understand how/why/when cancer cells communicate 15:33 – On the critical cancer relevance of how proteins and chemicals used in communication are used to ‘signal’ from one cell to another and within individual cells 19:03 – On working towards a new understanding of cell communication 22:33 – “I think these are the biggest open questions when it comes to blood cancers…” 24:06 – How a deeper understanding of Notch is an important step towards better treatments for cancer patients 27:19 – How her American Cancer Society research grant application was selected by a donor group for funding and what it was like to find out that her work was funded 30:34 – How ACS funding has impacted her research and career goals 32:34 – A message for other women considering a career in science and bringing your whole self into the lab

HPV, or Human Papillomavirus, is a common virus that can cause six types of cancer. While there is no treatment for HPV, there is a vaccine that can prevent it. The HPV vaccine works best when given between ages 9 and 12, for boys and girls, and it is safe, effective, and long-lasting. Jenny Grandis, MD, is at the forefront of translational research in head and neck cancer. She joined the podcast to talk about the prevalence of HPV-associated head and neck cancers, why they can be hard to detect, why the side effects can be so devastating, and why prevention through vaccination is so important. She was joined on the podcast by Adrienne Murr, a high school student who recently completed a summer internship in the Grandis lab. Ms. Murr talked about what she took away from her experience in the lab. And she offered helpful advice for parents talking to their children about HPV vaccination. She wrote an op-ed on the subject titled, "HPV is a threat to your children. Vaccines are not.” Jenny Grandis, MD, is the Robert K. Werbe Distinguished Professor in Head and Neck Cancer in the Department of Otolaryngology at the University of California, San Francisco. She was named an American Cancer Society Clinical Research Professor for her seminal contributions to the field. Adrienne Murr is a senior at Tamalpais High School in San Francisco, California. Fore more information about HPV vaccination, visit: https://www.cancer.org/healthy/hpv-vaccine.html 5:18 – On the association of head and neck cancers with infection by the human papillomavirus (HPV) 6:52 – The increasing prevalence of HPV-associated head and neck cancers 9:51 – Why HPV-associated head and neck cancers are hard to detect 11:15 – How they are treated, and why the side effects can be problematic 14:07 – Prevention is the answer 15:28 – On why the vaccine needs to be administered at ages 9-12 18:14 – What it was like for Adrienne to work in Jenny’s lab 19:54 – How her experience in the lab changed her perspective on the HPV vaccine 21:59 – Why it is so important for girls AND boys to get the vaccine 25:42 – How parents can talk to their children about HPV vaccination, and some helpful resources to help parents communicate the importance of the vaccine 28:51 – On the strange but ultimately delightful experience of mentoring a high school student during a pandemic 30:57 – How her experience interning in Dr. Grandis’s lab informed an op-ed Adrienne wrote, "HPV is a threat to your children. Vaccines are not.” 33:26 – How funding from the American Cancer Society has impacted Dr. Grandis and her research 36:30 – Wonderful advice from Adrienne for other young women interested in a research career

American Cancer Society scientists recently released a new report, “Blueprint for cancer research: Critical gaps and opportunities,” that sought to highlight the work needed to develop better tools and strategies to limit cancer as a major health concern. Our guest, Lynne Elmore, PhD— Senior Scientific Director of Cell Biology and Preclinical Cancer Research at the American Cancer Society—led the effort to “integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence‐based approaches for all patients with cancer and for all communities.” The full article, “Blueprint for cancer research: Critical gaps and opportunities,” can be found at: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21652 All eight ACS blueprint articles are available here: https://acsjournals.onlinelibrary.wiley.com/doi/toc/10.3322/(ISSN)1542-4863.ACS_Cancer_Control_Blueprints 2:37 – Dr. Lynne Elmore of the Extramural Discovery Science team at the American Cancer Society 3:58 – The role of this team in funding cancer research around the country, launching the careers of cancer scientists, and giving hope to cancer patients and caregivers 7:12 – What were the motivations behind writing “Blueprint for Cancer Research: Critical Gaps and Opportunities?” 10:41 – The collaborative approach taken to producing the Blueprint, which incorporated diverse perspectives from scientists and clinicians on the front lines of cancer treatment 15:30 – What major themes emerged from this Blueprint? 20:40 – The most surprising observations in the Blueprint, such as early detection developments related to liquid biopsies 23:59 – What she hopes readers will take away from the Blueprint, and three ways that cancer patients and survivors can help advance research 30:01 – Important parallels between the Blueprint and the work of the Extramural Discovery Science Department at the American Cancer Society 34:45 – A message she’d like to share with cancer patients, caregivers and survivors

Early detection of cancer through screening reduces mortality from cancers of the colon and rectum, breast, uterine cervix, and lung (see https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines.html). Cancer mortality has declined in recent decades in part due to progress in cancer screening technologies, awareness, research, and the general population’s improved uptake in screening services. But far too many individuals for whom screening is recommended remain unscreened, and this situation has been aggravated by the substantial decline in cancer screening resulting from the COVID-19 pandemic. Moreover, the pandemic-related disruptions will likely exacerbate existing disparities in cancer screening and survival across groups of people who have systemically experienced social or economic obstacles to screening and care. Deana Baptiste, PhD, MPH—the American Cancer Society’s Director of Guideline Development Process—joined the TheoryLab podcast to talk about why cancer screening remains a public health priority and an essential service. REFERENCES: ACS Guidance on Cancer Screening During COVID-19: https://www.acs4ccc.org/acs-guidance-on-cancer-screening-during-covid-19/ American Cancer Society screening guidelines: https://www.cancer.org/healthy/find-cancer-early/cancer-screening-guidelines.html 3:44 – The role that screening plays in decreasing cancer mortality 6:08 – Pre-pandemic, were we where we wanted to be as a country in terms of cancer screening? 9:05 – On the concerning drop in cancer screening resulting from the COVID-19 pandemic 13:58 – Have measures that have been put into place to make hospitals safe for patients during the pandemic had unintended consequences on screening? 20:09 – Why cancer screening remains a public health priority and essential service 24:36 – Strategies to get cancer screening back on track 31:42 – How screening disparities have been impacted by the pandemic 35:47 – Some ways to deal with the “unprecedented backlog in cancer screening” 43:10 – Lessons learned from the pandemic that will inform our ability to better deliver cancer screenings appropriately, safely, and equitably

Every year the American Cancer Society estimates the number of new cancer cases and deaths that will occur nationally and in each state. Published annually since 1951, “Cancer Facts & Figures” provides the most current information about cancer. These widely cited projections serve as a basis for research, are a valued resource by policymakers, and are also readily understood by the public. How many new cancer cases are there projected to be in 2021? What are the current cancer incidence, mortality, and survival statistics? What’s the latest information on cancer symptoms and risk factors? The just-released “Cancer Facts & Figures 2021” and “Cancer Statistics 2021” provide a comprehensive breakdown of the most up-to-date cancer statistics. This year’s report also includes a special section on cancer and COVID-19. To find Cancer Facts & Figures 2021, as well as slides and an interactive tool where you can dive deeper into the data, visit http://cancer.org/statistics Rebecca Siegel, MPH, is lead author of these publications. She is a cancer epidemiologist and Senior Scientific Director of Surveillance Research at the American Cancer Society. Ms. Siegel directs the production of 7 Facts & Figures publications and their accompanying scientific articles, including the Cancer Facts & Figures 2021, which was published January 12. Her other research focuses on disparities in cancer incidence and mortality with an emphasis on colorectal cancer, particularly early-onset disease. Her research contributed to a shift in the age at which the American Cancer Society recommends beginning colorectal cancer screening. 3:00 – Rebecca Siegel on Cancer Facts & Figures 2021 and Cancer Statistics 2021 4:54 – Where does this cancer data come from? 8:01 – The differences between Cancer Facts & Figures 2021 and Cancer Statistics 2021 10:30 – What makes these publications so important? 13:16 – On the importance of her team’s findings on early onset colorectal cancer, and how this research led to an update in guidelines on when to start screening 17:37 – Findings shared in the special section on COVID-19 and cancer 22:15 – On what findings surprised her in this year’s edition 24:47 – A hopeful takeaway from Cancer Facts & Figures 2021

NCI-designated Cancer Centers play leading roles in their communities through cancer research, cancer prevention and control, and clinical research. Being the director of a Cancer Center is a position of immense responsibility. Now imaging taking on that role during a pandemic. Joann Sweasy, PhD—the inaugural holder of the Nancy C. and Craig M. Berge Endowed Chair for the Director of the University of Arizona Cancer Center—joined the podcast to talk about her approach to the position and how the Cancer Center has dealt with the challenges presented by COVID-19. She also talked about her lab’s ongoing research into DNA damage and repair and how that relates to cancer. And she spoke at length about mentoring, women in science issues, and what it was like to study under Dr. Evelyn Witkin, one of the leading cancer researchers of our time. Dr. Witkin helped change our understanding of DNA repair. In 1946, when the American Cancer Society’s extramural research program was launched, Dr. Witkin was one of the first female researchers funded by ACS. 3:33 – Joann Sweasy, PhD, Inaugural holder of the Nancy C. and Craig M. Berge Endowed Chair for the Director of the University of Arizona Cancer Center 5:09 – On the role that NCI-Designated Cancer Centers play in cancer prevention, clinical service, and research 8:32 – How her colleagues at the Cancer Center have responded to the COVID-19 pandemic to continue supporting cancer patients, caregivers, and researchers 10:07 – On how the pandemic has provided some unexpected silver linings 13:19 – Some of the ways that research into COVID-19 will benefit cancer patients 17:14 – On her lab’s research into DNA damage and repair and why this is critical to understanding cancer 20:08 – Recent research findings in her lab that she’s most excited about 25:08 – What it was like to train under the great Dr. Evelyn Witkin 28:08 – On some of the caregiving and work-life balance challenges faced by cancer researchers in 2020… 31:11 – …and how academic institutions and research funders could help 34:58 – Advice for young women pursuing a career in science 36:58 – The impact of ACS funding (and peer review) on her career 39:49 – A message she’d like to share with cancer patients, survivors, and caregivers

Dr. Stacey Finley develops mathematical models to better understand cancer, tumor growth, and the effectiveness of different therapies. Her team creates a mathematical representation of what’s happening in biology, so they can understand how reactions are happening in cells, how cells are interacting with one other, and how that influences the growth of a tumor. They can use that data to create simulations and make predictions about what could happen, all with the goal of finding more effective treatments for cancer patients. Using mathematical modeling, “we can try as many ideas as we can think of, in a shorter amount of time, with fewer resources, and with fewer dollars to spend, compared to doing experimental studies.” Dr. Finley provides the best explanation of mathematical modeling you’re likely to hear. But she also spoke at length about her approach to scientific mentoring and had wonderful advice for other young women of color who are aspiring scientists. Stacey Finley, PhD, is Associate Professor of Biomedical Engineering and the Gordon S. Marshall Early Career Chair at the University of Southern California. 3:51 – On systems biology and why it’s important to understand networks of reactions happening inside of cells instead of looking at one reaction at a time 5:38 – Why the immune system is a nice platform for looking at system-level behavior 8:22 – Mathematical modeling? What is that? 11:00 – Some great examples of how mathematical models are helpful to understanding cancer 15:20 – The process: use experimental data and clinical data to build a reliable mathematical model to make useful predictions; do simulations; make predictions; work with collaborators to test and validate the predictions; impact patient care 19:03 – An aspect of her research she’s particularly excited about 26:23 – Her approach to scientific mentoring and lessons she’s learned along the way 31:18 – Advice for aspiring mathematicians, scientists, and engineers who are young women of color 35:05 – Ways that she thinks funding agencies could make careers in cancer research more inclusive 40:01 – How ACS funding has impacted her research and career 45:04 – A message she’d like to share with people whose lives have been impacted by cancer

Lung squamous cell carcinoma (LSCC) is the 2nd most common sub-type of lung cancer, accounting for around 30% of lung cancer diagnoses. And it is a particularly deadly disease that’s characterized by poor therapeutic response, a high relapse rate, and poor prognosis. Furthermore, unlike other subtypes of lung cancer, to date there are no therapies to specifically target the LSCC subtype. Verline Justilien, PhD, has an American Cancer Society grant to study an oncogenic protein called Ect2. Too much of it is a bad thing, and the more you have of it as a LSCC patient, the worse your prognosis is. What if we could know which patients have a worse prognosis, so we could treat them more aggressively? What if a therapy could target Ect2? Dr. Justilien takes us through her very promising research into a kind of cancer where we urgently need progress. And she also Verline Justilien, PhD, is Assistant Professor of Cancer Biology at the Mayo Clinic. 3:28 – What is lung squamous cell carcinoma (LSCC)? 5:33 – A goal of precision medicine is targeting and treating specific tumor types; but no therapies are available that specifically treat LSCC. Dr. Justilien talks about why that is. 8:40 – What is an oncogene? 9:53 – Why is the Ect2 oncogene so important… 11:54 - …and why is it so important in this sub-type of lung cancer? 14:33 – Could the levels of Ect2 in a lung squamous cell carcinoma patient be used to predict patient outcomes? 17:49 – On how her team is trying to target Ect2 therapeutically 19:04 – How ACS funding has impacted her research 21:08 –What advice would she have given to her high school self to encourage her to accomplish her dreams? 23:14 – While female college students of color report interest in STEM majors at an equivalent rate as white women students, they remain the least represented group in STEM. What could be done to attract and retain more women of color in research? How could ACS help? 26:39 – A message she’d like to share with cancer patients, caregivers, and survivors

The number of adults aged 85 and older is expected to triple by 2060, due in large part to better treatments and a decline in tobacco use. Because cancer risk increases with age, demand for cancer care in this population will continue to grow. William Dale, MD, PhD, joined the podcast to talk about the needs of older adults who are cancer patients and how we can better meet them. He also talked about “The Elephant in the Room,” a film executive produced by Dr. Dale and his wife that depicts the real-life experiences of Bonnie Freeman, who was a nurse practitioner at City of Hope. Ms. Freeman, who wrote the screenplay for the film, tragically passed away shortly before the film’s release. The film, which is available on Amazon Prime, is about a “comical nurse practitioner who treats his patients in an unconventional way, is challenged by a tough and stubborn patient, but is determined to show him the bright side, even when the end is so close.” Amazon Prime: https://www.amazon.com/Elephant-Room-Niko-Vitacco/dp/B08GCNTZXQ IMDB: https://www.imdb.com/title/tt8857090/ William Dale, MD, PhD, is Chair of Supportive Care Medicine and Director of the Center for Cancer and Aging Research at City of Hope, a comprehensive cancer center near Los Angeles. 4:49 – Unmet needs for older adults who are cancer patients 9:47 – On barriers preventing senior cancer patients from enrolling in clinical trials 13:34 – What strategies might decrease these barriers? 17:27 – Misconceptions and opportunities for impact in the field of palliative care 22:02 – On “The Elephant in the Room” 24:40 – How he hopes the film could help advance palliative care, and how it draws on the real-life experiences of nurse practitioners and social workers at City of Hope 29:36 – How to find “The Elephant in the Room” on Amazon Prime, and how a number of colleagues in medicine have commented on its realism 32:21 – How the American Cancer Society has impacted his research and clinical care 37:15 – Current research pursuits that he’s most excited about 42:19 – A message he’d like to share with cancer patients, survivors and caregivers

Clinical trials are the key step in advancing potential new cancer treatments out of the lab and into the clinic. Patient participation in trials is crucial to this success. But only a small fraction of patients end up enrolling in a cancer clinical trial due to barriers that make participation difficult or even impossible. As a result, approximately 20% of cancer clinical trials fail due to insufficient patient enrollment. Understanding and addressing these barriers is critical to accelerating progress in cancer research. Mark Fleury, PhD, is Policy Principal at ACS CAN – the American Cancer Society Cancer Action Network (https://www.fightcancer.org/). Dr. Fleury joined the podcast to help us understand where we are falling short and how we can reduce these barriers to patient enrollment in clinical trials. 5:36 – What is ACS CAN? 7:55 – A recent piece of cancer-related legislation where ACS CAN was involved that he is particularly proud of 13:07 – Why clinical trials in cancer research are so important to patients 16:23 – On barriers to clinical trial enrollment: ACS CAN resources note that “approximately 20% of cancer clinical trials fail due to insufficient patient enrollment.” Why are we falling short? 22:50 – Some of the recommendations ACS CAN has helped identify that would reduce barriers to enrollment in cancer clinical trials 27:04 – How clinical trial matching services could be improved 32:38 – On disparities in clinical trial participation

Resistance to treatment – it’s one of the most important issues in cancer research. If cancer cells aren’t killed during treatment, either because they weren’t affected or because they changed enough to survive the treatment, it could lead to cancer recurrence. Tuomas Tammela, MD, PhD, has an American Cancer Society grant to explore resistance to treatment in lung adenocarcinoma, the most common subtype of lung cancer. In this conversation he walks us through new findings from his lab on the “highly plastic state” of certain cells in tumors. He explains how this relates to tumor heterogeneity, why this is a problem in lung cancer and other cancer types, and how it could be used in combination therapies. Tuomas Tammela, MD, PhD, is Assistant Member at the Sloan Kettering Institute at Memorial Sloan-Kettering Cancer Center. 3:01 – What does it mean for cancer to become resistant to treatment? 5:24 – What does resistance to treatment mean in terms of the cellular makeup of a tumor? 7:21 – A helpful way to understand “tumor heterogeneity” 9:31 – What it means for cells to be in a “highly plastic state” and why that’s importance to treatment resistance and cancer progression 13:05 – Is the “highly plastic cell state” seen in different cancer types and… 14:46 – …could it be targeted therapeutically? 16:51 – How tumor heterogeneity impacts treatment resistance in lung cancer 20:42 - If later stage lung cancer tumors are more heterogenous, what could help us understand how to treat them? 25:12 – On how American Cancer Society funding has impacted his research 26:41 – A message he’d like to share with cancer patients and caregivers

It is no exaggeration to say that Jennifer Temel, MD, has helped change how cancer care is practiced. Through her research, she has shown that integrating palliative care and oncology care from the time of cancer diagnosis improves patient outcomes. This early integrated care model is now the standard of care in the United States and many other countries. Now, however, because it’s the standard of care, demand for early palliative care is so great that the palliative care workforce is unable to meet every patient’s needs. So Dr. Temel is now working to use novel healthcare technologies—such as telehealth and mobile apps—to deliver patient-centered palliative care to cancer patients and their families everywhere. Jennifer Temel, MD, is an American Cancer Society Clinical Research Professor. She is Professor of Medicine at Harvard Medical School and Director of the Cancer Outcomes Research Program at the Massachusetts General Hospital Cancer Center. 2:17 – On what motivated her to become an oncologist 3:20 – What is palliative care? How can palliative care differ from the care provided by an oncology clinician? 4:48 – On the importance of early palliative care for patients with serious cancers 7:06 – On her seminal research findings showing that integrating palliative care with oncology care leads to better outcomes 8:32 – How cancer caregivers are impacted by palliative care 10:21 – On how palliative care is typically offered, drawbacks to the current delivery system, and communicating well with patients and their families 16:30 – On being named an ACS Clinical Research Professor 17:40 – On the goals of her ACS-funded work: using healthcare technology to better support and inform cancer patients… 21:25 – …and the three technologies she’s focused on 28:35 – How the pandemic has impacted the need to be innovative in how palliative care is provided 32:49 – How ACS and the cancer community at large can help scale her findings 35:46 – A message she’d like to share with cancer patients and caregivers

Just as telemedicine is changing the ways in which primary care is delivered, much of cancer care can be delivered safely, effectively and less expensively from home. Penn Home Infusion Therapy has been providing infusion therapy at home for around two decades, but starting last year, in November 2019, just a few months before the pandemic started to complicate health care in America, Penn Medicine launched Cancer Care at Home. A joint initiative of the Penn Center for Cancer Care Innovation, the Center for Healthcare Innovation and the Division of Hematology and Oncology at Penn, the goal of the program is “to establish the home as a place where appropriate patients can receive appropriate care.” In this conversation, Dr. Justin Bekelman and Katherine Major describe the benefits of Cancer Care at Home, some of the barriers for home care that exist in America, and how the program navigated a 700% increase in patient care when the Covid-19 pandemic took hold in America. Justin Bekelman, MD, a former American Cancer Society grantee, is Professor of Radiation Oncology and Medical Ethics and Health Policy as well as the Director of the Penn Center for Cancer Care Innovation. Katherine Major, MSN, RN, CHPN, is a registered nurse and a director of Penn Medicine at Home. She oversees the Penn Home Palliative Care and Penn Home Infusion Therapy programs. 6:09 – The benefits of delivering cancer care at home 9:17 – On how cancer care is delivered at home – What treatments can be administered safely and effectively at home? What symptoms can be managed in home environments? 14:43 – On sorting out who can be treated at home and who needs to be treated in a clinical setting 18:54 – On the staffing resources needed to safely provide cancer care at home 22:35 – On some of the roadblocks patients, caregivers and care teams need to navigate 27:14 – How the Cancer Care at Home program navigated the difficult period when the pandemic startd to take hold in America 31:42 – Some wonderful patient stories 36:47 – How ACS funding helped Dr. Bekelman “take science from inception to scale” 39:18 – A message they’d like to share with cancer patients, caregivers, and survivors

Dawn Hershman, MD, MS, was recently named an American Cancer Society Clinical Research Professor for the seminal contributions she’s made to the field of cancer health services research. Her contributions to the field are so wide ranging and impactful, they defy summary. From identifying patients who are at risk of receiving poor cancer care and intervening to improve their outcomes, to conducting trials to improve patients’ compliance with care, to examining strategies to manage cancer-related toxicities, Dr. Hershman’s work has had a remarkable impact on cancer patients’ quality of care and quality of life. She has also been a leader in health equity and cancer disparities, demonstrating why Black cancer patients may have worse outcomes and improving clinical trial recruitment and retention of Black patients. Dawn Hershman, MD, MS, is Professor of Medicine and Epidemiology at Columbia University Medical Center. 3:49 – What kinds of things can stand in the way of patients receiving optimal cancer therapy? 8:01 – On breast cancer patients who are more at risk than others for poor treatment and outcomes 11:55 – On what the cancer treatment community should be doing NOW to improve quality of care for breast cancer patients and narrow disparities 15:12 – On the many different ways we could improve quality of life for breast cancer patients 18:36 – Why QOL issues can be challenging for patients and physicians 23:07 – On the significant impact that the expense of cancer treatment can have on breast cancer patients, and possible cost reduction strategies 26:02 – On what she hopes to accomplish with her new American Cancer Society ACS funding… 28:09 – …and how she hopes her research could help patients 29:44 – How organizations such as the American Cancer Society could help disseminate her findings 32:19 – A message she’d like to share with cancer patients, survivors and caregivers