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Event Detail (Archived)

Lineage Plasticity in Prostate Cancer

Event Details

Friday Lecture Series
Charles L. Sawyers, M.D., Marie-Josée and Henry Kravis Chair in Human Oncology and Pathogenesis, chairman, human oncology and pathogenesis program, Memorial Sloan Kettering Cancer Center; investigator, Howard Hughes Medical Institute

The most common mechanism of acquired resistance to targeted cancer therapies is alteration of the drug target -- typically through mutation or amplification or through bypass of the signaling pathway blockade. There is growing evidence of a conceptually distinct mechanism in which the tumor cells escape growth inhibition by shifting their lineage such that the drug target is no longer essential for the proliferation of that cell type. Dr. Sawyers will present recent work from his laboratory showing how prostate cancers can escape from hormone therapy by undergoing an identity change from androgen-dependent luminal epithelial cells to more basal-like epithelial cells. This lineage plasticity occurs in the setting of combined loss of function mutations in RB and TP53 and is mediated in part by the reprogramming transcription factor SOX2. In addition, his lab has found that several prostate cancer driver genes, such as FOXA1, ERF, and ERG, also perturb normal basal-luminal differentiation programs. Thus, lineage plasticity can have a role in prostate cancer initiation as well as in acquired resistance, with important clinical implications for the timing and context in which hormone therapy should be used.

Dr. Sawyers received a BA from Princeton University in 1981 and an M.D. from Johns Hopkins University School of Medicine in 1985, followed by an internal medicine residency at UCSF. He became a Howard Hughes Medical Institute Investigator in 2002 while at UCLA, and then moved to Memorial Sloan Kettering Cancer Center in 2006 where he currently serves as the Chair of the Human Oncology and Pathogenesis Program.

Dr. Sawyers shared the 2009 Lasker-DeBakey Clinical Medical Research Award for the development of the ABL kinase inhibitor imatinib for patients with chronic myeloid leukemia and the second generation ABL inhibitor dasatinib to overcome imatinib resistance. He received the 2013 Breakthrough Prize in Life Sciences, the 2013 Taubman Prize for Excellence in Translational Medical Science and the 2015 BBVA Knowledge Award in Biomedicine.

Justin Sloboda
(212) 327-7785
Open to
Sohail Tavazoie
Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge
Justin Sloboda
(212) 327-7785

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