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De Novo Palmitate Synthesis Supports Oncogenic Signalling and Tumor Growth Through Diverse Mechanisms: Implications for FASN-Targeted Therapeutics

Timothy S. Heuer

Palmitate, the enzymatic product of fatty acid synthase (FASN), provides a substrate for the synthesis of longand short-chain fatty acids. Many recent studies have expanded our knowledge about the roles palmitate and lipid synthesis play in tumor cell biology beyond supporting energy metabolism and membrane building. The recent article described cell biology and pharmacology studies using a novel, selective small molecule FASN inhibitor, TVB-3166. They demonstrated that FASN inhibition disrupts oncogenic signalling and tumor growth in xenograft models through inhibition of pathways that include Wnt/beta-catenin and expression of c-Myc: potent oncogenes historically recalcitrant to direct pharmacological inhibition. Discussed here are how these findings advance our mechanistic understanding of the diverse biological roles of palmitate and its integration into various signalling pathways driving tumor cell proliferation and survival. These insights highlight the promising potential of selective, potent FASN inhibitors as a novel therapeutic strategy for cancer and other illnesses.