2010 UALC
Trever Bivona, MD, PhD
University of California, San Francisco
Research Project:
Characterization of Mechanisms Underlying EGFR Oncogene Dependence
Summary:
EGFR-targeted therapies are initially very successful in patients with EGFR-activating mutations, but those patients eventually become resistant. In some cases, patients develop an additional mutation to the EGFR gene; however, there are a number of systemic changes that occur within the cell that can contribute to growth signaling, even when EGFR is blocked. Dr. Bivona hypothesizes that additional genetic mutations in the Fas-NFkB pathway can circumvent dependence on EGFR signaling and allow tumor growth even after EGFR is blocked. Using inhibitors to block this pathway, Dr. Bivona hopes to increase responsiveness to EGFR-targeting drugs with this new combination and improve treatment of EGFR-positive lung cancer.
More Content:
Interim Report
Dr. Bivona has made substantial progress during the first year of funding in each aim of the project. He and his team have determined that increased Fas-NFkB signaling promotes resistance to EGFR inhibitors in lung cancer, and showed that increased NFkB predicts for decreased response to EGFR inhibitors in lung cancer patients. He and his team unexpectedly discovered that several additional genes not previously implicated in EGFR inhibitor resistance also regulate NFkB signaling and promote resistance to EGFR inhibitors in lung cancer. Dr. Bivona is currently conducting followup studies on these genes and hope to report new findings in the next year.
Notable Accomplishments
Dr. Bivona published his research in Nature and Nature Medicine. Dr. Bivona was recruited to start his own research group at several leading academic medical centers and cancer centers around the country. He joined the UCSF Comprehensive Cancer Center in July 2011 as a faculty member to start his lung cancer research group. Dr. Bivona has received follow-on funding from the National Lung Cancer Partnership and the NIH Director’s New Innovator Awards, totaling $1.5 million over five years.