Anti-cancer drugs targeting fatty acid synthase (FAS).
Anti-cancer drugs targeting fatty acid synthase (FAS).
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DOI：
10.2174/157489212799972891
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发表时间：
2012-05
影响因子：
2.8
通讯作者：
P. Pandey;Wen Liu;F. Xing;K. Fukuda;K. Watabe
中科院分区：
文献类型：
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作者：
P. Pandey;Wen Liu;F. Xing;K. Fukuda;K. Watabe
脂肪酸合成酶（FAS）是脂肪酸生物合成途径中的关键酶，催化脂质的从头合成。FAS在正常成人组织中的表达通常非常低或检测不到，因为获得的大部分脂肪酸来自饮食来源，而尽管有足够的营养脂质供应，但其在癌细胞中显著上调。FAS的激活为快速增殖的肿瘤细胞提供足够量的脂质用于膜生物发生，并赋予生长和存活优势，可能作为代谢癌基因起作用。重要的是，使用药理学FAS抑制剂抑制癌细胞中的FAS导致肿瘤细胞通过凋亡死亡，而正常细胞具有抗性。由于FAS的这种差异表达，该酶的抑制剂对肿瘤细胞具有选择性毒性，因此FAS被认为是癌症的有吸引力的治疗靶点。几种FAS抑制剂已经获得专利和商业化;然而，这些FAS抑制剂的潜在毒性仍有待于在临床试验中测试。在这篇综述中，我们讨论了一些有效的FAS抑制剂沿着专利信息，抗癌作用的机制，以及开发更特异，更有效的FAS抑制剂，副作用更低，有望在不久的将来成为抗癌治疗。
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.