McIlwain C C, Townsend D M, Tew K D
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
Oncogene. 2006 Mar 13;25(11):1639-48. doi: 10.1038/sj.onc.1209373.
The super family of glutathione S-transferases (GSTs) is composed of multiple isozymes with significant evidence of functional polymorphic variation. Over the last three decades, data from cancer studies have linked aberrant expression of GST isozymes with the development and expression of resistance to a variety of chemicals, including cancer drugs. This review addresses how differences in the human GST isozyme expression patterns influence cancer susceptibility, prognosis and treatment. In addition to the well-characterized catalytic activity, recent evidence has shown that certain GST isozymes can regulate mitogen-activated protein kinases or can facilitate the addition of glutathione to cysteine residues in target proteins (S-glutathionylation). These multiple functionalities have contributed to the recent efforts to target GSTs with novel small molecule therapeutics. Presently, at least two drugs are in late-stage clinical testing. The evolving functions of GST and their divergent expression patterns in individuals make them an attractive target for drug discovery.
谷胱甘肽S-转移酶（GSTs）超家族由多种同工酶组成，有充分证据表明其存在功能多态性变异。在过去三十年中，癌症研究数据已将GST同工酶的异常表达与对多种化学物质（包括抗癌药物）的耐药性发展和表达联系起来。本综述探讨了人类GST同工酶表达模式的差异如何影响癌症易感性、预后和治疗。除了已充分表征的催化活性外，最近的证据表明，某些GST同工酶可以调节丝裂原活化蛋白激酶，或促进谷胱甘肽添加到靶蛋白中的半胱氨酸残基上（S-谷胱甘肽化）。这些多种功能促使最近人们努力用新型小分子疗法靶向GSTs。目前，至少有两种药物正处于后期临床试验阶段。GST不断演变的功能及其在个体中的不同表达模式使其成为药物发现的一个有吸引力的靶点。
