Clem B F, O'Neal J, Klarer A C, Telang S, Chesney J
From the Department of Biochemistry and Molecular Genetics, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40292
Department of Medicine, Washington University, 660 South Euclid Ave, St. Louis, MO 63110.
QJM. 2016 Jun;109(6):367-72. doi: 10.1093/qjmed/hcv181. Epub 2015 Oct 1.
Glucose and glutamine metabolism in cancer cells are markedly elevated relative to non-transformed normal cells. This metabolic reprogramming enables the production of adenosine triphosphate and the anabolic precursors needed for survival, growth and motility. The recent observations that mutant oncogenic proteins and the loss of tumor suppressors activate key metabolic enzymes suggest that selective inhibition of these enzymes may yield effective cancer therapeutics with acceptable toxicities. In support of this concept, pre-clinical studies of small molecule antagonists of several metabolic enzymes in tumor-bearing mice have demonstrated reasonable therapeutic indices. We will review the rationale for targeting metabolic enzymes as a strategy to treat cancer and will detail the results of several recent clinical trials of metabolic inhibitors in advanced cancer patients.
与未转化的正常细胞相比，癌细胞中的葡萄糖和谷氨酰胺代谢显著增强。这种代谢重编程能够产生三磷酸腺苷以及生存、生长和迁移所需的合成代谢前体。最近的观察结果表明，突变的致癌蛋白和肿瘤抑制因子的缺失会激活关键代谢酶，这表明选择性抑制这些酶可能会产生毒性可接受的有效癌症治疗方法。为支持这一概念，在荷瘤小鼠中对几种代谢酶的小分子拮抗剂进行的临床前研究已证明了合理的治疗指数。我们将综述将代谢酶作为治疗癌症的策略的基本原理，并详细介绍最近在晚期癌症患者中进行的几项代谢抑制剂临床试验的结果。
