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谷胱甘肽 S-转移酶:癌症研究概述。

Glutathione S-transferases: an overview in cancer research.

机构信息

Universidade Estadual de Santa Cruz, Departamento de Ciências da Saúde, Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Ilhéus, Bahia 45662-900, Brazil.

出版信息

Expert Opin Drug Metab Toxicol. 2010 Feb;6(2):153-70. doi: 10.1517/17425250903427980.

Abstract

IMPORTANCE OF THE FIELD

The Glutathione S-transferases (GSTs) have advanced beyond the classic view of their role in metabolism and are encouraging scientists to assess new approaches to cancer risk characterization and chemotherapy resistance and are opening up exciting possibilities in drug discovery.

AREAS COVERED IN THIS REVIEW

In this review, the most recent knowledge about the impact of GST genetic polymorphisms in human's cancer susceptibility, ethnic differences in the effects of risk factors and the rise of the GSTs as important targets for drug development are presented. In this context, the ethnic distribution of GST alleles in different populations, which is an important concept that is being incorporated in epidemiologic studies of cancer risk and environmental exposure, was also evaluated. We present up-to-date information about the new generation of GST-activated cytotoxic prodrugs based on GST overexpression in tumor-acquired drug resistance and the newest results of clinical trials.

WHAT THE READER WILL GAIN

A critical approach of the major advances in research of GST, underlining the new advances of GST genes polymorphisms in cancer susceptibility and target for therapeutic intervention.

TAKE HOME MESSAGE

Although polygenic factors are involved in increased risk of cancer, the interindividual GST variability plays a central role in reduce cells exposure to carcinogens.

摘要

重要性领域

谷胱甘肽 S-转移酶 (GSTs) 的作用已经超越了其在代谢中的经典作用,这促使科学家们评估癌症风险特征和化疗耐药性的新方法,并为药物发现开辟了令人兴奋的可能性。

本篇综述涵盖

在这篇综述中,介绍了 GST 基因多态性对人类癌症易感性的影响、风险因素的影响在不同种族之间的差异以及 GST 作为药物开发重要靶点的最新知识。在这方面,还评估了 GST 等位基因在不同人群中的种族分布,这是癌症风险和环境暴露的流行病学研究中正在纳入的一个重要概念。我们提供了 GST 过表达导致肿瘤获得性药物耐药性的 GST 激活细胞毒性前药的新一代的最新信息,以及临床试验的最新结果。

读者将获得

对 GST 研究主要进展的批判性方法,强调 GST 基因多态性在癌症易感性和治疗干预靶点方面的新进展。

重要信息

尽管多基因因素与癌症风险增加有关,但 GST 的个体间变异性在降低细胞暴露于致癌物方面起着核心作用。

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