Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, Georgia.
Cancer. 2014 Mar 15;120(6):774-80. doi: 10.1002/cncr.28501. Epub 2013 Dec 2.
Nearly a century ago, Otto Warburg made the astute observation that the metabolic properties of cancer cells differ markedly from those of normal cells. Several decades passed before the concept of exploiting cancer cell metabolism came into clinical practice with the advent of chemotherapy, the underlying principle of which is to target rapidly dividing cells by interfering with critical processes that are all, on some level, driven by cell metabolism. Although chemotherapy can be quite effective, success rates are highly variable and the adverse effects associated with treatment often outweigh the benefits due to the fact that chemotherapy is indiscriminately cytotoxic against all rapidly dividing cells, cancerous or healthy. During the past several years, a more intricate understanding of cancer cell metabolism has permitted the development of targeted therapies that aim to specifically target cancer cells and spare healthy tissue by exploiting the altered metabolism of cancer cells. The identification of new metabolic targets and the subsequent development of small-molecule inhibitors of metabolic enzymes have demonstrated the utility and promise of targeting cancer cell metabolism as an anticancer strategy. This review summarizes recent advances in the identification and characterization of several metabolic enzymes as emerging anticancer targets.
近一个世纪前，奥托·瓦尔堡（Otto Warburg）敏锐地观察到癌细胞的代谢特性与正常细胞有明显的不同。几十年过去了，随着化疗的出现，利用癌细胞代谢的概念才进入临床实践，其基本原理是通过干扰所有在某种程度上都由细胞代谢驱动的关键过程，靶向快速分裂的细胞。虽然化疗可能非常有效，但成功率差异很大，并且由于化疗不分青红皂白地对所有快速分裂的细胞（包括癌细胞和健康细胞）具有细胞毒性，因此与治疗相关的不良反应常常超过其益处。在过去几年中，对癌细胞代谢的更深入理解使得靶向治疗得以发展，这些治疗方法旨在通过利用癌细胞代谢的改变来特异性地靶向癌细胞并保护健康组织。鉴定新的代谢靶点和随后开发代谢酶的小分子抑制剂已经证明了靶向癌细胞代谢作为抗癌策略的实用性和前景。本文综述了近年来在鉴定和表征几种代谢酶作为新兴抗癌靶点方面的进展。
