Inhibition of Fatty Acid Synthase (FAS): A New Drug for Breast Cancer Chemoprevention

Fatty acid synthase FAS has shown promise as a new target for breast cancer therapy. FAS is the primary enzyme responsible for the de novo synthesis of fatty acid and is highly expressed in most common human cancers, including breast, colorectal, prostate, ovary, and lung. Moreover, high levels of FAS have been found in cancer precursor lesions of the breast, prostate, and colon. In contrast, dietary fat down-regulates FAS and fatty acid synthesis in most normal tissues. To test the effect of FAS inhibition in cancer, we have developed a novel, chemically stable, small molecule FAS inhibitor, C75, that induces apoptosis in human breast cancer cells in vitro and in vivo. C75 has shown significant anti-tumor effect against MCF-7 human breast cancer xenografts in athymic mice. In light of these data, we have demonstrated that inhibition of FAS delays or eliminates mammary cancer in the neu-N transgenic mouse mammary cancer model. Moreover, treatment reduced the expression of genes known to be involved in neu signal transduction.