This session will familiarize participants with the application and utility of molecular oncology testing. Participants learn the fundamental features of molecular testing platforms as faculty review clinical scenarios in which molecular testing is appropriate. In addition, participants will learn to interpret molecular test results and explain their clinical significance. Featured panels include sarcoma, hematology, neuro-oncology, and RNA sequencing.
Introduction to NGS Targeted Testing
Benjamin R. Kipp, Ph.D.
The Utility of Molecular Testing in Soft Tissue Pathology Karen Fritchie, M.D., Mayo Clinic
Karen Fritchie, M.D. is an Associate Professor of Laboratory Medicine and Pathology at Mayo Clinic with a special and long-standing interest in lipomatous soft tissue neoplasms. She received her M.D. from the University of Medicine and Dentistry of New Jersey and was an AP/CP resident at the University of North Carolina, where she served as Chief Resident during her fourth year. Subsequently, she completed a Surgical Pathology fellowship at the University of North Carolina followed by a Bone and Soft Tissue Fellowship at the Cleveland Clinic.
Dr. Fritchie has an avid interest in teaching and has been an active educator at the resident/fellow level within the Mayo Clinic, where she currently serves as the Surgical Pathology Fellowship Program Director. She has presented numerous lectures and interactive tutorials in bone/soft tissue pathology at institutions and conferences on a national and international level. Dr. Fritchie is an author on over 75 publications and serves as an ad-hoc reviewer for many journals. ...
Clinical Utility of Next Generation Sequencing in Myeloid Neoplasms Rong He, M.D., Mayo Clinic
Dr. Rong He is a board-certified hematopathologist at Mayo Clinic in Rochester, MN. She is a consultant and associate professor in the Division of Hematopathology, Department of Laboratory Medicine and Pathology, and a co-director of the Molecular Hematopathology Laboratory. Besides her slides-based hematopathology diagnostic work incorporating morphology, flow cytometry, and cytogenetic and molecular findings, Dr. He oversees the molecular hematopathology lab. She has developed and improved multiple molecular tests for hematologic disorders, using various technologies including next generation sequencing. She has also designed and implemented value-based, cost-effective reflexive molecular testing algorithms for Mayo Clinic’s clinical practice. Her professional interests center on diagnostic pathology of myeloid neoplasms, molecular test development for hematologic neoplasm diagnostics and prognostics, and appropriate, cost-effective test utilization. Dr. He is a member of the molecular analysis committee of the International Society of Laboratory Hematology in addition to multiple other professional organizations including American Society of Hematology, College of American Pathologists, and United States and Canadian Academy of Pathology. She also serves as a reviewer for multiple scientific journals and the Mayo Clinic medical lead for the Mayo-Wuxi joint venture. ...
Aditya Raghunathan, M.D., M.P.H.
RNA-Seq for the Detection of Gene Fusions and Other Clinically Relevant Genetic Alterations in Tumors
Kevin C. Halling, M.D., Ph.D.
Introduction and Welcome Alan H. Bryce, M.D., Mayo Clinic
Alan H. Bryce, M.D., is a consultant in the Division of Hematology and Oncology, Department of Internal Medicine at Mayo Clinic in Arizona and serves as chair of the division. He currently serves as medical director of the Genomic Oncology Clinic at Mayo Clinic in Arizona. He holds the academic rank of associate professor of medicine, Mayo Clinic College of Medicine.
Dr. Bryce's research centers on understanding the genetic mutations of individual cancer cells in order to allow for a precise, targeted treatment strategy. The ultimate goal is for every patient to have their tumor biopsied and sequenced, resulting in a personalized treatment plan. In his leadership role with the Genomic Oncology Clinic, he utilizes whole genome sequencing of tumors to identify key driver mutations. This approach allows for precise targeting of a patient's tumor, leading to a greater chance of remission. Dr. Bryce participates in community outreach to underserved populations and has in interest in health disparities research.
Dr. Bryce has received numerous awards and honors, including the Excellence in Teaching Recognition Award, conferred by Mayo Medical School, the Young Investigator Award, conferred by the American Journal of Hematology; the Oncology Scholar in Training Award, conferred by the American Association of Cancer Research, Bristol-Myers Squibb; and the Outstanding Trainee Award, conferred by the Hematology/Oncology Fellowship Program, Mayo Clinic. He has been a member of the Mayo Clinic staff since 2011. ...
Past, Present and Future of Precision Medicine in Cancer Care Keith Stewart, M.B., Ch.B., Mayo Clinic
Dr. Keith Stewart, M.B., Ch.B, MBA, is a consultant in the Division of Hematology and Oncology, Department of Internal Medicine at Mayo Clinic. He currently serves as the Carlson and Nelson Endowed Director of the Mayo Clinic Center for Individualized Medicine and is recognized as the Vasek and Anna Maria Polak Professor of Cancer Research. Dr. Stewart’s current responsibilities at Mayo Clinic relate to the application of genomics to human health across the spectrum of discovery, translation and application to clinical practice. Dr. Stewart has served in several leadership roles across both research and clinical practice at Mayo Clinic, including as dean for research in Arizona, and as a member of the Arizona Executive Operations Team and Clinical Practice Committees. He has served on multiple boards for both non-profit and commercial organizations, including currently as a Non-Executive Board member with Genomics England and the Scientific Advisory Boards of Helix Inc., Veritas Genetics, Inc., and the Multiple Myeloma Research Foundation.
His own research interest is in the genomics and biology of myeloma and he has led numerous clinical trials of new drugs for this blood cancer. Dr. Stewart has over 25 years of sustained national funding for a laboratory research program and has authored over 300 journal articles and other written publications. He has served as an associate editor of Blood and ASH Clinical News. ...
Keynote: CAR-T TherapyYi Lin, M.D., Ph.D., Mayo Clinic
Under-diagnosis of Familial Cancer Syndromes and Faulty Clinical Guidelines Niloy Jewel Samadder, M.D., Mayo Clinic
Dr. Samadder’s focus is in the areas of hereditary cancer syndromes and endoscopic oncology. He directs the high risk cancer clinic at Mayo Clinic’s campus in Arizona, which provides genetic consultation and testing to patients with early onset cancer, rare cancers, and hereditary cancers. This practice provides clinical management to patients with an inherited cancer syndrome, including (but not limited to) those with Lynch syndrome, Familial Adenomatous Polyposis, MYH Associated Polyposis, Li Fraumeni syndrome, BRCA syndromes, or any other genetic cancer syndrome. This clinic provides patients with a single point of contact for genetic testing and cancer screenings. Dr. Samadder also leads multiple clinical trials using medications to prevent cancers in these patients. His efforts aim to increase genetic evaluation and testing of patients with cancer throughout Mayo Clinic.
Dr. Samadder’s early research involves diagnosis of hereditary cancer often changes treatment to an individualized approach shaped by a patient’s genetic makeup. Dr. Samadder, with the support of Mayo Clinic’s Center for Individualized Medicine, is moving toward testing all cancer patients for such inherited mutations — not just patients with cancer in their family tree. “If we knew that cancer was genetically predisposed, it can lead to unique options ensuring that treatments target the cancer and minimize side effects,” says Dr. Samadder.
Questions and Discussion with the Faculty
Genome-wide Germline Breast Cancer Pharmacogenomics Richard Weinshilboum, M.D., Mayo Clinic
Dr. Weinshilboum received B.A. and M.D. degrees from the University of Kansas, followed by residency training in Internal Medicine at the Massachusetts General Hospital in Boston, a Harvard teaching hospital. He was also a Pharmacology Research Associate at the National Institutes of Health (NIH) in the laboratory of Nobel Laureate Dr. Julius Axelrod. He is presently Professor of Pharmacology and Medicine and Dasburg Professor of Cancer Genomics Research at the Mayo Clinic and he co-directs the Pharmacogenomics Program of the Mayo Center for Individualized Medicine with his faculty colleague, Dr. Liewei Wang, MD-PhD. Dr. Weinshilboum’s research has focused on pharmacogenomics, with over 450 peer-reviewed manuscripts and an emphasis in recent decades on the application of genome-wide genomics and other “omics” techniques to study variation in drug response--especially the drug therapy of breast cancer and depression. He has received a series of major Awards in Clinical Pharmacology and Precision Medicine, and he has served on National Advisory Councils for two NIH Institutes, the National Institute for General Medical Sciences and the National Human Genome Research Institute—the NIH institute the led the Human Genome Project. ...
Genetic & Epigenetic Markers in RCC Thai H. Ho, M.D., Ph.D., Mayo Clinic
Evolutionary Biology of Tumors: Lessons from Pest Control and Ecology Carlo Maley, Ph.D., Arizona State University
Dr. Maley is a biologist who specializes in cancer, evolution and computational biology and works at the intersection of these fields. He and his research team apply evolutionary and ecological theory to three problems in cancer. First, they investigate neoplastic progression: the evolutionary dynamics among cells of a tumor that drive progression from normal tissue to malignant cancers. Second, they examine acquired therapeutic resistance; the evolutionary dynamics by which therapies select for resistance and fail to cure cancer. Third, they look into the evolution of cancer suppression mechanisms in large, long-lived animals such as elephants and whales (a problem called Peto’s Paradox). His team uses genomic data mining, phylogenetics, computational modeling and wet lab techniques to solve these problems. In their work, the research team focuses on developing better methods to prevent cancer and improve cancer management.
Dr. Maley’s research centers around evolution and the impact of evolutionary forces on cancer progression. He argues that ecological principles and statistics can predict neoplasm composition and rate of mutations. With the understanding that neoplasms evolve by natural selection and that each tumor exists in a unique microenvironment, Dr. Maley examines patterns in malignancy, therapeutic response, and resistance. ...
Questions and Discussion with the Faculty
Summary of the Day
Adjourn for Poster Session
Poster Session and Welcome Reception
Introduction Alan H. Bryce, M.D., Mayo ClinicKaren S. Anderson, M.D., Ph.D., Mayo Clinic/Arizona State University
Dr. Anderson is a physician scientist with a joint appointment at Arizona State University and at Mayo Clinic’s campus in Arizona. She is a medical oncologist who focuses on biomarker development and immunotherapy in breast cancer and actively conducts clinical trials in these areas. Additionally, she has identified new targets for future breast cancer vaccine development using next-generation sequencing and high-throughput functional genomics. She obtained her M.D. and Ph.D. from Duke University School of Medicine and completed her internship and residency at the Brigham and Women’s Hospital.. ...
Tumor Profiling by Cell Free DNAMinetta C. Liu, M.D., Mayo Clinic
Vaccines Keith L. Knutson, Ph.D., Mayo Clinic
Dr. Knutson is an expert in the field of cancer immunology, specifically with regard to breast and ovarian cancers. He is involved in the clinical development and testing of self-tumor antigen-specific vaccines, and actively contributes to clinical trials and translation. He frequently authors high-impact journal articles and gives presentations on his research nationally and internationally. In recognition of his work, Dr. Knutson has received many awards and honors, including the Young Investigator Award-Pharmingen, conferred by the American Association for Cancer Research, and the prestigious Howard Temin Award, conferred by the National Institutes of Health, National Cancer Institute. He is also recognized as the 2017 Investigator of the Year at Mayo Clinic’s campus in Florida. Dr. Knutson has several current and past memberships with professional organizations which include the Breast Cancer Research Program and the Ovarian Cancer Research Program of the United States Department of Defense, the Tumor Microenvironment Study Section of the U.S. National Institutes of Health Center for Scientific Review, and the Education and Training Committee for the Society for the Immunotherapy of Cancer. He is a Principal Investigator of the Artemis Project, National Breast Cancer Coalition, where he is leading efforts to produce prevention vaccines for breast cancer.
Dr. Knutson’s research team studies the physical effects of the vaccine and looks for whether it stimulates an immune response. In previous studies, they found a vaccine promoted mild responses typical of any vaccination. They also found that the vaccine promotes a measurable immune response in patients to the HER2 protein. Dr. Knutson will discuss the role of therapeutic vaccines in cancer care.
Immunotherapy in Lung Cancer Aaron S. Mansfield, M.D., Mayo Clinic
Dr. Mansfield is a medical oncologist with a focus on thoracic malignancies and early therapeutics. He was the first to describe the negative prognostic significance of PD-L1 expression in mesothelioma and led the discovery that chromosomal rearrangements have neo-antigenic potential. He is the principal investigator of many clinical trials and translational projects evaluating the ability of blood-based biomarkers to predict responses to immunotherapy. He also helped led accrual to the recent clinical trial that changed the practice of frontline therapy for patients with extensive stage small cell lung cancer. ...
Questions and Discussion with the Faculty
Optimizing the Manufacturing of Autologous Cell Therapies: the Road Less Traveled Michael Gustafson, Ph.D., Mayo Clinic
Dr. Michael Gustafson is a Senior Associate Consultant in the Division of Laboratory Medicine and Department of Laboratory Medicine and Pathology. He is an Assistant Professor of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, and Scientific Director of the Nyberg Human Cellular Therapy Laboratory at the Mayo Clinic Arizona Phoenix campus. His research focuses on the development and translation of cell and immune-based therapies for the treatment of cancer, autoimmunity, and other diseases into clinical trials. Additionally, he works to understand systemic immunity, how cancer alters the immune landscape in humans, and methods for tailoring the patient’s immune system to the most optimal cell and/or immune-based therapy. Dr. Gustafson received his undergraduate degree in Biology at North Park University in Chicago, and his PhD degree in Biomedical Sciences- Molecular Biology at the Mayo Clinic. He completed is post-doctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, WA. ...
Overcoming Challenges in CAR-T Cell Development for Solid TumorsDr. William Go, Ph.D., A2 Biotherapeutics
Next Gen CAR-T Cells / In Vivo CAR-T Cells Using Nano Particle VectorsMatthias Stephan, M.D., Ph.D., Fred Hutchinson Cancer Center
Dr. Stephan is a physician scientist at the Fred Hutchinson Cancer Research Center who works at the interface of materials science and immunology, designing synthetic materials that can be used as components of new cancer therapies that selectively modulate the immune system. His long-term goal is to make cancer immunotherapy more widely accessible and successful by creating off-the-shelf reagents that can rapidly boost the body's natural ability to fight cancer, moving synthetic immunomodulatory materials into routine clinical practice and shifting the treatment focus from broadly toxic chemotherapy and radical surgery to tumor-specific immunotherapies. Dr. Stephan demonstrated for the first time that immune T cells can be genetically engineered to self-stimulate when they encounter tumors, thereby enhancing anticancer immune responses. He also designed synthetic nanoparticles that can selectively deliver therapeutic drugs to tumors by smuggling them on the backs of tumor-seeking T cells, minimizing systemic drug toxicities. Currently, he continues to develop injectable nanoparticle reagents, including those that can rapidly program T cells to attack tumors. His ongoing research is focused on targeting melanoma, prostate, and ovarian cancers.
In-vivo T-cell targeting and reprogramming selectively edits lymphocyte targeting in vivo to slow or force cancer regression. Dr. Stephan’s research has been looking at finding treatment and next-generation options in lieu of complex procedures and costs involved in producing genetically modified lymphocytes. This presentation identifies opportunities for its use in precision cancer care.
Mechanisms of Escape in CAR-T Cell TherapySaar Gill, MD, PhD, University of Pennsylvania
Dr. Gill is a physician scientist and assistant professor of medicine at the University of Pennsylvania where he specializes in the treatment of patients with leukemia. His research interests include tumor immunology, CAR T cells, mouse models of human leukemia, adoptive cell therapy, and flow cytometry. His most recent research examines the use of genetically modified T cells in the treatment and management of hematologic malignancies such as leukemia and lymphoma. His findings have also been applied to other diseases including neurodegenerative disorders. ...
CAR-T Therapies for LymphomaJanuario E. Castro, M.D., Mayo Clinic
Dr. Castro has expertise in translational research and early-stage therapy development applied to hematologic malignancies with emphasis on cellular and stem cell therapy and gene immunotherapy. Dr. Castro focuses on translational research applied to the biology of cancer immunotherapy, discovery and optimization of novel antigens that can be used for cellular therapy, RNA splicing as a mechanism of gene and antigen diversity in cancer, and models of artificial intelligence applied to immunotherapy. His focus areas are cellular therapy for hematological cancer, cellular therapy for solid tumors, immune system response, early detection of side effects, and artificial intelligence and machine learning models applied in immuno-oncology.
CAR-T therapy for patients with lymphoma involves taking T-cells from patients and genetically modifying them to create Chimeric antigen receptors (CARs). Dr. Castro will share his experience in patient care and translation research in CAR-T therapy, working to develop better, more patient-friendly therapies for cancers including lymphoma.
CAR-T Cell Toxicities: Background, Mechanisms, and Interventions Marco L. Davila, M.D., Ph.D., Moffitt
Dr. Marco Davila is a medical oncologist that specializes in the treatment of patients with cell therapies. He received his medical degree from Duke University and medical training at the New York Presbyterian Weill Cornell Medical Center and Memorial Sloan Kettering Cancer Center. His clinical focus is on hematologic malignancies such as chronic lymphocytic leukemia, B cell Acute Lymphoblastic Leukemia (B-ALL), and Acute Myeloid Leukemia. He is appointed as an Associate Member in the Departments of Blood and Marrow Transplantation and Cellular Immunotherapy, as well as Immunology. He serves as the Medical Director of the Cell Therapy Facility overseeing cell manipulation and production for patient use, either investigative or as standard of care. As a translational physician-scientist he is engaged in both clinical and laboratory research. His research has helped usher in a new field of medical oncology by developing a novel cell engineered therapy for B-ALL and DLBCL. His current research is dedicated to developing and/or improving gene-engineered cell therapies that target cancer. The goal of this research is to identify optimal cell therapies that can then be evaluated in cancer patients.
The use of CAR-T therapy in patients is complicated by adverse events and potentially severe toxicities. Great efforts are being made to research how to reduce and predict these effects. Insights into recognition and management will be reviewed.
Clinical Management of Immune Checkpoint Inhibitor ToxicitiesLisa Kottschade, APRN, CNP, Mayo Clinic
Checkpoint-inhibition is an effective form of cancer management, however, it can be associated with significant toxicities and immune-related adverse events. These potentially life-threatening toxicities are unique from other cancer therapies such as chemotherapy. Guidelines for recognition and management will be reviewed.
Questions and Discussion with the Faculty
Applying Genomic Profiling to Breast CancerMinetta C. Liu, M.D., Mayo Clinic
Dr. Liu is a medical oncologist and translational researcher in the Department of Oncology and Department of Laboratory Medicine and Pathology at Mayo Clinic. Her clinical practice focuses on providing care to patients with breast cancer. Her laboratory interests focus on the development and implementation of blood-based biomarkers for all solid tumors. She leads several studies with clinical and correlative endpoints focused on the efficient development of reliable predictors of treatment outcomes. ...
Beyond EGFR, ALK, and ROS1: Applying NGS to Lung CancerAaron S. Mansfield, M.D., Mayo Clinic
Treatment Implications of Molecular Variation in Prostate CancerHimisha Beltran, M.D., Dana Farber Cancer Institute
Dr. Himisha Beltran is a medical oncologist and physician scientist at the Dana Farber Cancer Institute. Her clinical and research interests are in the areas of prostate cancer and precision oncology. Her lab has focused on understanding mechanisms of treatment resistance in advanced prostate cancer and has developed therapeutic targets and biomarkers for non-androgen receptor driven prostate cancer including neuroendocrine prostate cancer, an aggressive subtype of castration resistant prostate cancer. As recent Director of Clinical and Translational Research within the Weill Cornell Englander Institute for Precision Medicine (2013-2018) and now as newly appointed Director of Translational Research in Medical Oncology at the DFCI, Dr. Beltran works to develop molecularly based treatment approaches for patients including through the establishment of protocols for metastatic biospecimen collection, serial blood collection, and the use of next generation molecular assays. She has led the development and characterization of patient-derived tumor models including prostate cancer organoids and PDXs. She has also helped develop genomic and other molecular assays for clinical trials including a circulating tumor DNA platform for prostate cancer. ...
Questions and Discussion with the Faculty
Predictive Molecular Markers in Primary Cutaneous MelanomaAlexander Meves, MD, Mayo Clinic
KEYNOTE: Precision Therapy Through Functional Genomics in Hematologic MalignanciesJeffrey W. Tyner, Ph.D., OHSU
Dr. Jeffrey Tyner was born in West Lafayette, Indiana. He attended undergraduate school at Grinnell College in Grinnell, Iowa, and graduate school at Washington University in St. Louis. His graduate work, focusing on asthma and respiratory viral infections, was conducted under the mentorship of Dr. Michael Holtzman. For his post-doctoral fellowship, Jeff joined Dr. Brian Druker’s laboratory at Oregon Health & Science University (OHSU) where he studied molecular mechanisms of leukemogenesis. He is currently an Associate Professor in the Department of Cell & Developmental Biology at OHSU. Dr. Tyner’s research emphasizes: 1) identification of cancer-causing gene targets in cancer patients and 2) identification of patient-tailored, gene-targeted therapies. To accomplish these objectives, Dr. Tyner has spent the past decade developing and implementing a functional screening approach whereby primary cells from hem malignancy patients can be tested ex vivo for sensitivity to a library of small-molecule inhibitors. This assay has now been cumulatively applied to over 2,000 patient specimens, and this large data set has been leveraged to inform numerous findings that offer new diagnostic and therapeutic options for hem malignancy patients. ...
Questions and Discussion with the Faculty
Decision Support for Precision Oncology - Evolving from Monotherapy to Combinations Funda Meric-Bernstam, M.D., MD Anderson
Dr. Funda Meric-Bernstam is the Chair of the Department of Investigational Cancer Therapeutics - the Phase I Program, and the Medical Director of the Institute for Personalized Cancer Therapy at MD Anderson Cancer Center. She has a basic and translational research program that is focused on molecular therapeutics, delineating the mechanism of action of each agent targeting this pathway and the molecular alterations useful to prospectively identify patients who will benefit most from each agent, and optimal combination therapies with targeted therapies and novel immune-modulators. She is an active clinical trialist focused on Phase I trials, and rationale combinations, biomarker-driven therapy and immune-oncology. ...
KEYNOTE: What’s Next in the Treatment of Melanoma Antoni Ribas, M.D., Ph. D, University of California, Los Angeles
Dr. Ribas is a physician-scientist who conducts laboratory and clinical research in malignant melanoma, focusing on immune checkpoint blockade, gene engineered T cells, and BRAF targeted therapies at the University of California, Los Angeles. He has had a leading role in the clinical development and FDA approval of five new drugs for the treatment of metastatic melanoma. His National Cancer Institute, State of California and foundation-supported research laboratory develops models of disease to test new therapeutic options, studies mechanism of action of treatments in patients and the molecular mechanisms of therapy resistance. This work has allowed defining mechanisms of response and resistance to modern immunotherapies.
Dr. Ribas is an elected member of the American Society of Clinical Investigation, has a Doctor Honoris Causa from the University of Buenos Aires, co-led the Stand Up to Cancer -Cancer Research Institute -AACR Immunotherapy Dream Team with the Nobel Laureate James Allison, is the recipient of a NCI Outstanding Investigator Award, was profiled as one of the five Visionaries in Medicine by the New York Times on May 27, 2018, acknowledged as Great Immigrant by the Carnegie Foundation in the New York Times on July 4, 2018, and is the recipient of the 2014 AACR Richard and Hinda Rosenthal Award and the 2018 AACR-CRI Lloyd J. Old Award in Cancer Immunology. He currently serves as Professor of Medicine, Professor of Surgery, and Professor of Molecular and Medical Pharmacology at the University of California Los Angeles, Director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, Director of the Parker Institute for Cancer Immunotherapy Center at UCLA, Chair of the Melanoma Committee at SWOG, and President-elect of the America Association for Cancer Research. ...
Biliary Cancer: Transforming Rare Tumor Therapy through Target DiscoveryMitesh J. Borad, M.D., Mayo Clinic
Dr. Borad is an Associate Professor of Medicine and Director of Phase I Drug Development at Mayo Clinic Arizona. His research and clinical interests are in biomarker discovery and precision medicine for patients with biliary and liver cancers. Using whole genome analysis, his team works on discovery of new drug targets and delivery of precision medicine for patients with cholangiocarcinoma. Dr. Borad obtained his internal medicine training at Cedars-Sinai Medical Center and completed his medical oncology fellowship at Tulane University School of Medicine. ...
Stimulating Anti-Tumor Immunity Using Autologous Dendritic CellsAllan Dietz, Ph.D., Mayo Clinic
Questions and Discussion with the Faculty
Educational Summary with the Moderator