Charles Sawyers

Biosketch

Charles L. Sawyers is a Howard Hughes Medical Institute Investigator and Chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. He is the inaugural Chair of the GENIE (Genomics Evidence Neoplasia Information Exchange) Steering Committee, a genomics and clinical data sharing consortium established in 2015 by the American Association of Clinical Research (AACR). In his laboratory, Sawyers studies mechanisms of cancer drug resistance with an eye toward developing novel therapies. He co-discovered the antiandrogen drug enzalutamide that was approved by the FDA in 2012 for treatment of advanced prostate cancer. He 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. Sawyers is a member of the National Academy of Sciences, the National Academy of Medicine and the American Academy of Arts and Sciences. He was appointed to the National Cancer Advisory Board by President Obama and has served on the Board of Directors of Novartis since 2013. He received a BA from Princeton University in 1981 and an MD from Johns Hopkins University School of Medicine in 1985, followed by internal medicine residency at UCSF.

Research Interests

For over a decade, our group has concentrated on defining the molecular basis of prostate cancer and mechanisms of resistance to hormone therapy. This work has focused on the role of the androgen receptor in disease progression, even when tumors progress to the hormone-refractory stage. After demonstrating that higher levels of androgen receptor are necessary and su?cient to confer resistance to current antiandrogens, we collaborated with UCLA chemist Michael Jung to discover a small molecule inhibitor, enzalutamide, that targets the increased levels of androgen receptor found in hormone refractory disease through a novel mechanism. This AR inhibitor was approved for use in men with castration-resistant prostate cancer in 2012. A second compound, apalutamide, was approved for use in 2018 to delay prostate cancer metastasis in certain at-risk patients. Our current projects share the common goal of deciphering mechanisms of resistance to antiandrogen therapies and are grouped under the major themes of: crosstalk between AR and common molecular lesions in human prostate cancer (e.g. PTEN loss, TMPRSS2-ERG gene fusions and FOXA1 mutations); understanding AR structure and function; lineage plasticity in prostate tumors; and the prostate tumor microenvironment. We have developed several unique models to study prostate cancer initiation and progression, including genetically defined mouse models and primary prostate organoid culture. Our recent studies have focused on combining these tools with single cell analysis technologies to study genetic changes and tumor-host cell interactions in the prostate.