Protease Profiling in Prostate Cancer
Annual rept. 1 May 2002-30 Apr 2003
BURNHAM INST LA JOLLA CA
Pagination or Media Count:
Prostate cancer PCa is a leading cause of death in men in the United States 1. If detected early, when the tumor is still confined to the prostate, there are a number of treatment regimens that lead to good prognosis. However, if the tumor escapes the prostate prior to diagnosis, patient prognosis is poor. The objective of the proposed study was to identity serine hydrolases that are aberrantly regulated in PCa, and that contribute to progression of the disease. To accomplish this objective we undertook a unique approach, called activity-based protein profiling. In this method, a chemical probe comprised of a warhead and a detection reagent, are used to covalently tag the active site of an enzyme. Using this strategy we have identified a number of novel serine hydrolases that are expressed in prostate cancer. Of special importance is an enzyme called fatty acid synthase, which contains a serine hydrolase domain. We have identified lead inhibitors of this domain of fatty acid synthase, and demonstrated that one of these inhibitors is able to block the growth of tumors in mouse models of prostate cancer.
- Medicine and Medical Research