Sarah Cannon Research Institute, Nashville, Tennessee.
Clin Cancer Res. 2015 Dec 15;21(24):5434-8. doi: 10.1158/1078-0432.CCR-15-0126. Epub 2015 Oct 30.
Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer.
靶向肿瘤代谢的治疗方法代表了癌症治疗的一个新领域。特别是，癌细胞依赖于脂质的生成，脂质对于细胞膜合成、蛋白质修饰以及许多致癌信号转导酶的定位都是必不可少的。由于脂肪酸是这些重要脂质的组成部分，脂肪酸合酶（FASN）成为一个独特的肿瘤治疗靶点。FASN 抑制剂正在进行临床前研究，并开始向首次人体试验过渡。早期一代的 FASN 抑制剂已在临床前进行了研究，但由于其药理学特性和副作用谱而受到限制。新一代的分子，包括 GSK2194069、JNJ-54302833、IPI-9119 和 TVB-2640，正在开发中，但只有 TVB-2640 已进入临床阶段。FASN 抑制，无论是单独使用还是联合使用，都有望成为癌症患者的一种新的治疗方法。
