Targeting glucose metabolism in patients with cancer.
Targeting glucose metabolism in patients with cancer.
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作者：
Elf SE;Chen J
近一个世纪前，奥托·沃伯格敏锐地观察到癌细胞的代谢特性与正常细胞显著不同。几十年后，随着化疗的出现，利用癌细胞新陈代谢的概念进入临床实践，其基本原理是通过干扰在某种程度上都由细胞新陈代谢驱动的关键过程来靶向快速分裂细胞。虽然化疗可能非常有效，但成功率是高度可变的，而且由于化疗对所有快速分裂的细胞(无论是癌细胞还是健康细胞)都具有不分青红皂白的细胞毒性，与治疗相关的不良反应往往超过了好处。在过去的几年里，对癌细胞代谢的更复杂的了解使得靶向疗法的开发成为可能，这种疗法旨在通过利用癌细胞代谢的改变来专门针对癌细胞并节省健康组织。新的代谢靶点的发现和随后代谢酶小分子抑制剂的开发已经证明了靶向肿瘤细胞代谢作为一种抗癌策略的有效性和前景。本文综述了几种新陈代谢酶作为新的抗癌靶点的鉴定和表征的最新进展。
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.