Xenograft Studies of Fatty Acid Synthesis Inhibition as Novel Therapy for Breast Cancer

This grant proposes to study the effect of fatty acid synthesis inhibition in human breast cancer xenografts using C75, a novel inhibitor of fatty acid synthesis. C75 has now been shown to have significant anti-tumor activity against the MCF7 human breast cancer xenograft without apparent toxicity to normal proliferating cells. Studies of the mechanisms of cancer cell death from C75 have implicated high levels of malonyl-CoA as the trigger of apoptosis induced by fatty acid synthase inhibition. This is a novel mechanism for generation of apoptosis which may act directly at the mitochondria and will only be operative in cancer cells with high levels of fatty acid synthase. Given that fatty acid synthase is expressed at high levels in many common human cancers and their precursor lesions, this therapeutic strategy may have significant impact on future cancer treatment.