Targeting KRAS for cancer therapy
August 11, 2017
Frank McCormick, PhD, FRS
UCSF Helen Diller Family Comprehensive Cancer Center
KRAS proteins play a major role in human cancer. To target the KRAS protein directly, we have used tethering to identify compounds that covalently bind at two key residues, one which affects KRAS membrane localization, and another at a site unique to KRAS amongst other RAS proteins. We have also screened for molecules that cause allosteric changes in KRAS detected by a novel biophysical technique called Second Harmonic Generation. Dr. McCormick will discuss how these approaches are being developed and prospects for treating cancer using these, and other, KRAS inhibitors.
Frank McCormick, PhD, FRS, is a Professor at the UCSF Helen Diller Family Comprehensive Cancer Center. Prior to joining the UCSF faculty, Dr. McCormick pursued cancer-related work with several Bay Area biotechnology firms and held positions with Cetus Corporation (Director of Molecular Biology, 1981-1990; Vice President of Research, 1990-1991) and Chiron Corporation, where he was Vice President of Research from 1991 to 1992. In 1992 he founded Onyx Pharmaceuticals, a company dedicated to developing new cancer therapies, and served as its Chief Scientific Officer until 1996. At Onyx Pharmaceuticals, he initiated and led drug discovery efforts that led to the approval of Sorafenib in 2005 for treatment of renal cell cancer, and for liver cancer in 2007, and the approval of ONYX-015 in 2006 in China for treatment of nasopharyngeal cancer. Sorafenib is being tested in multiple indications worldwide. In addition, Dr. McCormick’s group led to the identification of the CDK4 kinase inhibitor, Palbociclib, approved for treating advanced breast cancer. Dr. McCormick’s current research interests center on the fundamental differences between normal and cancer cells that can allow the discovery of novel therapeutic strategies.
Dr. McCormick holds the David A. Wood Chair of Tumor Biology and Cancer Research at UCSF. Dr. McCormick is the author of over 320 scientific publications and holds more than 20 issued patents. He was Director of the Helen Diller Family Comprehensive Cancer Center from 1997 to 2014. He also served as President, 2012-2013, for the American Association for Cancer Research (AACR). Since 2013 he has taken a leadership role at the Frederick National Lab for Cancer Research, overseeing an NCI supported national effort to develop therapies against Ras-driven cancers. These cancers include most pancreatic cancers, and many colorectal and lung cancers, and are amongst the most difficult cancers to treat.