Pat Brown talks about his path to becoming a physician and scientist, the importance of a bench-to-bedside-back-to-bench approach in drug development, and targeted cancer therapy. Using his work in leukemia as an example, Pat talks about how changes at the level of DNA sequence change proteins and can lead to the development of cancer, and how scientists can use this knowledge to develop specific cancer treatments.
Works cited in this conversation:
The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee
Janet Rowley and her work on cancer genetics
FLT3 inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer, in the European Journal of Cancer, March 2004
The biology and targeting of FLT3 in pediatric leukemia, in Frontiers in Oncology, September 2014
Episode highlights:
*Susan introduces Pat [1:58];
*Pat talks about his journey to becoming a physician and scientist focusing on pediatric leukemia [5:08];
*What is leukemia? Pat gives us an overview [8:46];
*Why leukemia has been at the forefront of cancer research and treatment [11:58];
*Pat’s early research and clinical work in leukemia [13:38];
*When, how, and why cancer treatment shifted from a one-size-fits-all approach to something more targeted [15:45];
*Some of the specifics of Pat’s work — what is FLT3? Why is it important in leukemia? [21:12];
*Pat’s work in developing clinical trials for treatments for children with leukemia — bench to bedside and back again [28:00];
*Success with the small molecule lestaurtinib, a first-generation FLT3 inhibitor [30:10];
*Pat’s group partnered with another company to produce a monoclonal antibody that could target FLT3 [31:12];
*Main challenge with both treatments (and challenge with all cancer therapies) is cancer developing resistance to treatment — people try to prevent resistance with multimodal treatments [32:20];
*Leads to the idea of personalized therapy — in each person, what are the genetic characteristics driving the cancer and can those be targeted with a cocktail tailored to that person? [35:40];
*Liquid biopsy’s potential in helping us see solid tumor cancers earlier and more comprehensively [36:58];
*Pat’s reflections on working in “translational medicine” — as a physician and a scientist — and the importance of bedside to bench as well as bench to bedside [39:21];
*How working as a scientist in academia is different from working in industry [43:25];
*What Pat is working on now, and his hopes for a decade or two out [50:04];
*High school science portion of the episode — Focusing on leukemia as an example, Pat tells us how changes in the DNA sequence of a gene can result in cancer. This connects to one of the Next Generation High School Science Standards in Life Science, which states that students should be able to construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells [55:23];
*Pat shares a memory from high school science [1:02:43];
*Pat’s advice to high school students today who are interested in science [1:04:05]
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