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Treść dostarczona przez TheoryLab and American Cancer Society. Cała zawartość podcastów, w tym odcinki, grafika i opisy podcastów, jest przesyłana i udostępniana bezpośrednio przez TheoryLab and American Cancer Society lub jego partnera na platformie podcastów. Jeśli uważasz, że ktoś wykorzystuje Twoje dzieło chronione prawem autorskim bez Twojej zgody, możesz postępować zgodnie z procedurą opisaną tutaj https://pl.player.fm/legal.
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Treść dostarczona przez TheoryLab and American Cancer Society. Cała zawartość podcastów, w tym odcinki, grafika i opisy podcastów, jest przesyłana i udostępniana bezpośrednio przez TheoryLab and American Cancer Society lub jego partnera na platformie podcastów. Jeśli uważasz, że ktoś wykorzystuje Twoje dzieło chronione prawem autorskim bez Twojej zgody, możesz postępować zgodnie z procedurą opisaną tutaj https://pl.player.fm/legal.
American Cancer Society scientists and grantees discuss the most critical questions in cancer research -- in language that we can all understand.
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Treść dostarczona przez TheoryLab and American Cancer Society. Cała zawartość podcastów, w tym odcinki, grafika i opisy podcastów, jest przesyłana i udostępniana bezpośrednio przez TheoryLab and American Cancer Society lub jego partnera na platformie podcastów. Jeśli uważasz, że ktoś wykorzystuje Twoje dzieło chronione prawem autorskim bez Twojej zgody, możesz postępować zgodnie z procedurą opisaną tutaj https://pl.player.fm/legal.
American Cancer Society scientists and grantees discuss the most critical questions in cancer research -- in language that we can all understand.
…
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1 Improving treatment of inflammatory breast cancer 57:33
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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…
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1 Journal Club: Recent findings in cancer immunotherapy 33:32
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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…
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1 The rise of mental health distress during the COVID-19 pandemic 24:14
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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…
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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…
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1 Targeted therapies, drug resistance, and two recent cancer research publications 34:55
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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…
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1 “Holding Hope for Cancer Patients with Serious Illness” 21:23
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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…
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1 What causes small cell lung cancer growth and resistance? 28:46
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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…
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1 Improving our understanding of risk factors for breast cancer sub-types 37:37
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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…
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1 Fixing prescription drug coverage and reducing the financial burden of cancer 44:40
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“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…
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1 Maximizing what's learned from clinical trials in children 42:34
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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…
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1 “Overstretched & Overlooked: Solving challenges faced by early-career scientists after the pandemic” 45:29
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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…
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1 Catching the problem early: The early stages of lung cancer initiation & melanoma drug resistance 31:49
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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…
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1 Under pressure: Compression and crowding inside cancer cells 36:55
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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…
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1 Modulating the immune response to cancer & using metabolic routes in leukemia to our advantage 27:14
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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…
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1 Tricking cancer cells into taking drugs & improving drug delivery strategies for precision medicines 27:57
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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…
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