title: Anti-cancer drugs targeting fatty acid synthase (FAS).
abstract: Fatty acid synthase (FAS) is a key enzyme of the fatty acid biosynthetic pathway which catalyzes de novo lipid synthesis. FAS expression in normal adult tissues is generally very low or undetectable as majority of fatty acids obtained are from dietary sources, whereas it is significantly upregulated in cancer cells despite adequate nutritional lipid supply. Activation of FAS provides rapidly proliferating tumor cells sufficient amount of lipids for membrane biogenesis and confers growth and survival advantage possibly acting as a metabolic oncogene. Importantly, inhibition of FAS in cancer cells using the pharmacological FAS inhibitors results in tumor cell death by apoptosis whereas normal cells are resistant. Due to this differential expression of FAS, the inhibitors of this enzyme are selectively toxic to tumor cells and therefore FAS is considered an attractive therapeutic target for cancer. Several FAS inhibitors are already patented and commercially available; however, the potential toxicity of these FAS inhibitors remains to be tested in clinical trials. In this review, we discuss some of the potent FAS inhibitors along with their patent information, the mechanism of anti-cancer effects and the development of more specific and potent FAS inhibitors with lower side effects that are expected to emerge as anti-cancer treatment in the near future.
authors.affiliation: Department of Medical Microbiology, Immunology & Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge St. P.O. Box 19626, Springfield, IL 62794-9626, USA.
authors.forename: Puspa R
authors.initials: PR
authors.lastname: Pandey
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054872:Fatty Acid Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010330:Patents as Topic; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D054872:Fatty Acid Synthesis Inhibitors; D064429:Fatty Acid Synthases