William A. Weiss, M.D., Ph.D.
Professor of Neurology, Pediatrics, and Neurosurgery
University of California, San Francisco

EGFR is a signal which, in excessive amounts, contributes to uncontrollable cell growth in many types of cancer.  Several drugs which target EGFR were launched with high hopes, but their impact on patients has been disappointingly modest.  SWCRF-funded scientists have figured out how to change that and make the drugs more effective, perhaps without increasing side effects.

With support from the SWCRF, Dr. William Weiss, a physician scientist focused on these signaling pathways in brain cancer, collaborated with Dr. Kevan Shokat, a chemist, to examine why the anti-EGFR drugs failed to inhibit proliferation of cancer cells in patients.  The team of scientists detailed how excess EGFR promotes growth of glioblastoma, a brain cancer which has not responded significantly to the use of EGFR-inhibiting drugs and for which more effective treatments are needed.

The team, along with Dr. Albert Baldwin, another SWCRF-funded researcher, has already developed a new generation of EGFR inhibitors which appear to work more effectively than the ones currently in use because they block the EGFR signal more completely.  With this paper, they have identified another malfunctioning signaling pathway (protein kinase C ) which plays a critical role in the cell proliferation resulting from excess EGFR.  Both signals promote cancer when they are produced in excess of amounts required for normal cell growth.  Therefore, it is predicted that combining drugs which inhibit the two separate malfunctioning signals will enhance the effectiveness of cancer treatment in patients and, at the same time, may produce minimal side effects because the normal healthy cells are not dependent on this excess signal.