// May 7, 2019
Our guest today is Dr. Duane Mitchell, the Phyllis Kottler Friedman Professor in the Department of Neurosurgery at the University of Florida College of Medicine.
He’s also the co-director of the university’s Preston A. Wells Jr. Center for Brain Tumor Therapy and Director of the Brain Tumor Immunotherapy Program.
Duane and Dawn have been friends since their days at Duke University where they served on the Institutional Review Board together. Duane got his medical degree and doctorate at Duke and then joined the faculty, where he spent the next decade before moving to the University of Florida in 2013.
Duane and his team at Florida are among the world leaders in the uphill battle to find ways to treat glioblastoma, an aggressive form of brain cancer that affects about 13,000 Americans annually. It’s the disease that recently took the life of Senator John McCain. People who are diagnosed with glioblastoma typically live for less than two years.
Show notes:[00:03:00] Duane explains the story behind his “quote of the week” tradition, where every Monday morning he share’s a quote with his colleagues in his research group. [00:03:43] Ken asks if it is true that one of Duane’s favorite quotes comes from Mark Twain: “I have never let my schooling interfere with my education.” [00:04:13] Dawn asks if it is true that by the sixth grade Duane had decided he was going to become a doctor. [00:04:52] Duane talks about his decision to attend Rutgers College. [00:05:37] Duane explains how reading Stephen Rosenberg’s book “The Transformed Cell” heavily impacted him during his time at Rutgers. [00:06:43] Dawn mentions that she and Duane met at Duke University, and how this almost didn’t happen because Duane was originally going to attend another university for med school. [00:07:55] Dawn explains that after receiving his MD and Ph.D. from Duke, Duane went on to serve in numerous faculty positions for the next 12 years. During this time, Duane became known as a trailblazer in the application and research of immunotherapy for cancer, particularly brain tumors. Dawn asks Duane for an overview of the role that immunotherapy plays in the treatment of brain tumors. [00:09:30] Duane explains how in 2013 he joined the faculty at the University of Florida and managed to bring his entire team from Duke with him. [00:10:47] Duane has acquired considerable clinical and translational research experience as a principle investigator on seven first-in-human protocols through FDA approved clinical trials. Dawn points out that at Florida, Duane and his team offer unique clinical options for adult and pediatric malignant brain tumor patients. She asks Duane to explain, in depth, the work that he and his do at Florida. [00:12:11] Duane gives an overview of the types of brain tumor and what some of the more common tumor types are. [00:14:09] Dawn asks why Duane chose to specialize in glioblastoma, or GBM, an aggressive form of brain cancer that kills 15,000 Americans eachyear. [00:15:16] Ken asks what characteristics of GBM make those particular types of tumors so difficult to treat. [00:16:17] Duane talks about the standard of care for these malignant brain tumors. [00:18:36] Dawn asks if immunotherapy is a stand-alone approach for treating brain tumors, or if it is administered in conjunction with standard therapy. She goes on to asks if changes to the immune system through radiation or chemotherapy have a negative effect on immunotherapy. [00:21:20] Dawn asks if recent findings about the nervous system’s immune system, and the new-found interconnectedness between the glymphatic system and the lymphatic system impact immunotherapy approaches for brain tumors. [00:23:02] Ken asks how the immune system is naturally equipped to fight cancer. [00:25:36] Dawn explains that the (PD)-1/PD-L1 pathway, otherwise known as Programmed Cell Death, is an immune resistance mechanism that tumor cells exhibit to dampen immune response. Dawn asks about the efficacy of a new class of immunotherapy drugs called immune checkpoint inhibitors that block these signals and allow immune cells to be more effective in fighting the tumor. [00:28:11] Dawn mentions that Duane is helping to lead a health-organized coalition known as the ReMission Alliance, which is a University of Florida initiative that brings together neuro-oncology experts from institutions across the U.S. and Canada. [00:29:32] Ken mentions stories, both anecdotal and found in the literature, of the ketogenic diet having a beneficial effect in fighting cancer. He asks if Duane has given thought to the role of HDAC, given that BHB is an HDAC inhibitor, and that perhaps in addition to the energetic effects of ketone bodies, another benefit of the ketogenic diet in cancer is its signaling effects. [00:31:17] Ken mentions a recent paper in Nature Communications that describes how Duane and his colleagues at Florida have discovered a new use of stem cells that could clear a revolutionary pathway to make immunotherapy drugs effective in treating brain cancer. [00:33:25] Duane explains how cancer vaccines work. [00:34:39] Duane describes his study investigating personalized brain tumor-targeting vaccines for treatment of pediatric medulloblastoma. [00:35:50] Dawn asks about Duane’s clinical trial using an enhanced vaccine credited with significantly extending the lives of multiple glioblastoma patients. [00:37:36] Ken asks what the survival rates are for glioblastoma. [00:39:20] Heterogeneity, which is to say that is there can be a variety of distinct microenvironments with varying populations of neoplastic cells and collections of tissue-specific resident and recruited stromal cell types, can significantly impact response to immune therapy. Given this, Dawn asks if there is an effective tumor microenvironment on response to immunotherapy. [00:40:56] Duane talks about the mechanics and feasibility of the use of nanoparticles to administer cancer antigens to immune cells by crossing the blood brain barrier. [00:42:26] Ken asks if there are genetic or epigenetic factors that influence immunotherapy response. [00:44:38] Ken asks about the gut microbiome and if it has any influence on response to immunotherapy. [00:46:51] Ken mentions an earlier STEM-Talk Guest who specializes in microbiome, Alessio Fasano, interviewed in episode 20 of STEM-Talk. [00:47:56] Duane talks about what he sees as exciting coming down the line in brain tumor treatment. [00:50:15] Dawn asks about the impact that the National Cancer Act has had on cancer research, and our efforts to reduce cancer mortality in America. [00:52:52] Duane ends the interview with advice for aspiring researchers and physicians.