Targeting Fatty Acid Synthase To Inhibit Tumor Growth And Overcome Taxane Resistance

Aberrant metabolism mechanisms are a well-established hallmark of cancer. Exploiting tumor metabolism as a therapeutic target is being actively pursued. De novo synthesis of fatty acids by fatty acid synthase (FASN) is a particularly attractive mechanism to target because increased lipid synthesis is associated with more aggressive tumor. In particular, our work focuses on the reformulation of orlistat, an FDA-approved lipase inhibitor that also inhibits the thioesterase domain of FASN. We report on the rationale, synthesis, efficacy, delivery, and limitations of a novel nanoparticle formulation of orlistat in the goal of targeting the FASN pathway.