Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression.

摘要: BACKGROUND Fatty acid synthase (FAS) performs the anabolic conversion of dietary carbohydrate or protein to fat. FAS expression is low in most normal tissues, but elevated many human cancers, including androgen-sensitive and androgen-independent prostate cancer. METHODS Immunohistochemical evaluation was performed cancer specimens under various states androgen ablation. In vitro vivo models were evaluated for activity androgenic androgen-depleted conditions, tested sensitivity antimetabolite drugs that target fatty synthesis. RESULTS While responsive, it persisted reactivated carcinoma after ablation, high 82% lethal tumors examined at autopsy. Similar patterns synthesis seen cell culture xenograft cancer. Pharmacologic inhibition resulted a dose-dependent reduction tumor growth these models, fourfold an with little associated toxicity. CONCLUSIONS The data suggest expression/FA provides important functional aspect malignant phenotype cancer, perhaps supporting survival. may be upregulated by alternate signaling pathways withdrawal. The re-emergence during development independence demonstrate serve as novel therapy Prostate 47:102–110, 2001. © 2001 Wiley-Liss, Inc.