Fatty acid synthase inhibitors: new directions for oncology

Abstract

Fatty acid synthase (FASN) is the enzyme that catalyzes the de novo synthesis of fatty acids in cells. Because of the strong expression in many cancers, FASN is an attractive and tractable target for therapeutic intervention. The discovery and development of pharmacologic agents that block FASN activity highlight the promise of these anticancer compounds. FASN inhibitors have also proven to be invaluable in developing a better understanding of the contribution of FASN and fatty acid synthesis to tumor cells. Recent advances in the development of crystal structures of FASN have provided promise towards the development of novel FASN inhibitors. This review outlines the preclinical development of FASN inhibitors, their antitumor effects and the strategies underway to develop novel inhibitors.

Keywords::

• C75
• cerulenin
• fatty acid synthesis
• flavonoids
• inhibitor
• metabolism, orlistat
• thiolactomycin

Acknowledgements

Research on FASN by the Kridel and Lowther laboratories was supported by developmental funds from Wake Forest University School of Medicine, the Kulynych Interdisciplinary Cancer Research Fund, the Department of Defense Prostate Cancer Research Program (W81XWH-05-1-0065 and W81XWH-07-1-0024) and from the National Cancer Institute (CA114104). Views and opinions of and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. The authors would like to thanks J Lewis, PhD and J Schmitt, PhD for their helpful comments on the manuscript.

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