Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer.
©2015 American Association for Cancer Research.