Title:Anti-Cancer Drugs Targeting Fatty Acid Synthase (FAS)
Volume: 7
Issue: 2
Author(s): Puspa R. Pandey, Wen Liu, Fei Xing, Koji Fukuda and Kounosuke Watabe
Affiliation:
Keywords:
Apoptosis, fatty acid synthase, FAS inhibitors, lipogenesis, patents
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.
