BioScience Forum Presents
Gideon Bollag, Ph.D.
Senior Vice President of Research
Plexxikon "Kinase Drug Development"
WhenWednesday, September 15, 2010 6:00 PM - 9:00 PM WhereThe Clarion Hotel 401 East Millbrae Avenue, Millbrae, CA 94030
Abstract
Kinase inhibitors are gaining prominence in the fight to treat a variety of human cancers, and different approaches targeting two kinase pathways will be discussed: RAF and FMS.
The identification of RAF kinases (A-, B-, and C-RAF) as important effectors of the RAS oncogene subsequently led to drug discovery efforts to identify potent inhibitors of RAF kinase. One such discovery project led to the identification of sorafenib, a potent inhibitor of C-RAF kinase. Despite the successful development of sorafenib as a therapeutic option for patients with metastatic kidney and liver cancers, an understanding of the mechanistic role of C-RAF inhibition remains enigmatic even ten years since its initial discovery. In the intervening years, identification of the BRAF oncogene led to renewed efforts to discover RAF pathway inhibitors. Structure-guided optimization yielded PLX4032, a potent and selective inhibitor of oncogenic B-RAF kinase activity. In preclinical cellular and in vivo studies, this inhibitor demonstrates potent anti-cancer activity against tumors bearing oncogenic BRAF mutations, while showing no effect on tumors lacking BRAF mutations. In non-clinical toxicology studies, there were no adverse effects even at the highest doses administered, confirming the high degree of selectivity of this compound. Given the favorable pharmacology, this inhibitor advanced to human clinical trials in cancer patients. Early clinical data have now revealed anti-cancer activity in patients with metastatic melanoma. Indeed, significant tumor regressions have been confirmed in patients whose tumors harbor the BRAF oncogene, and the promise of PLX4032 was highlighted in the New York Times earlier this year.
An additional approach to treat cancers targets the tumor microenvironment. We have discovered a selective inhibitor of FMS, the receptor for CSF-1 which controls differentiation of macrophages, osteoclasts, and microglial cells. By blocking the activity of these host cells, our inhibitor has shown anti-tumor activity in mouse models of breast cancer and bone cancer pain. This compound is also currently in clinical testing in cancer patients.
BiographyDr. Bollag has served as senior vice president of research at Plexxikon since June 2008, and has more than 20 years of biotechnology drug discovery experience. He previously served as vice president of discovery biology since 2004 and joined Plexxikon as senior director of drug discovery in 2002. Prior to Plexxikon, he helped build drug discovery capabilities at Syrrx, Inc., where he was the director of cellular pharmacology. Before Syrrx, he held escalating positions at Onyx Pharmaceuticals, initially as one of the founding scientists and eventually as senior director of small molecule therapeutics. While there, Dr. Bollag was involved in the Onyx collaboration with Bayer to discover BAY 43-9006, a kinase inhibitor that is now approved for the treatment of renal cell and hepatocellular carcinoma and marketed under the trade name Nexavar®. Prior to Onyx, Dr. Bollag worked with Dr. Frank McCormick at Cetus, Inc. Dr. Bollag earned his Ph.D. in biochemistry from the University of California, Berkeley.
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Agenda6:00 pm - 7 pm networking7:00 pm - 8 pm dinner8:00 pm - 9 pm presentation
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Event Registration ($3 service fee will apply) General Pre-Registration $45.00General On-Site Registration $55.00Student Pre-Registration $35.00Student On-Site Registration $45.00
Pre-Registration ends Monday, September 13th, at 9 pm
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