脂肪酸代谢与肿瘤靶向治疗新途径

Fatty acid metabolism and novel targeted therapy of cancer

脂肪酸从头合成的增强是肿瘤细胞具有标志性的代谢异常之一。从头合成是肿瘤细胞获得脂肪酸的主要途径,并参与肿瘤细胞转化、增殖和迁移的各个方面。因此,脂肪酸合成通路的相关酶成为合理的抗肿瘤治疗靶点。然而,最近的研究发现,抑制肿瘤细胞内源性脂肪酸合成而产生的抗肿瘤作用,可被添加外源性脂肪酸所逆转。此外,大量摄入膳食脂肪是导致某些肿瘤进展及预后不良的潜在危险因素。因此,除了从头合成途径产生的脂肪酸,某些肿瘤细胞还可以利用脂肪分解途径产生的脂肪酸来维持自身的增殖和存活。脂肪分解产生的脂肪酸可能是肿瘤细胞获得脂肪酸的另一来源,脂肪分解途径将为抗肿瘤治疗提供新的靶点。本文就目前对肿瘤细胞脂代谢变化的认识进行综述,探索靶向脂代谢通路的抗肿瘤治疗的新理论和新方向。

Enhanced de novo fatty acid （FA） synthesis is one of the most important metabolic hallmarkers of cancer cells. Increased FA synthesis has been considered as the major mean of FA acquisition in cancer cells, and involves various aspects of tumorigenesis and the proliferation and migration of tumor cells, therefore, enzymes in FA synthesis pathway become potential targets for anti-cancer therapy. However, recent studies have found that the cytotoxic effects caused by inhibition of endogenous FA synthesis in tumor cells can be reversed by exogenous FA supplementation. Moreover, a high intake of dietary fat is considered to be a risk factor of tumor progression and poor prognosis of certain cancers. Accordingly, besides de novo FA synthesis, certain tumor cells can acquire FA from lipolytic pathway to remain their proliferation and vital. Lipolysis may be another source for FA acquisition in tumor cells and raises the possibility of novel therapeutic targets. This review focuses on the current understanding of lipid metabolism for cancer, in order to explore new targets against lipid metabolism pathway for anti-cancer therapy.