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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.
Acknowledgements
The authors acknowledge the contributions of all investigators in the glutathione S-transferase field, particularly those who have worked with and generated data presented in this paper. The authors also acknowledge the relevant research grants from the National Council for Research (Brazil) (Conselho Nacional de Pesquisa-CNPq) and The Foundation for Research Support of the Bahia State (Fundação de Amparo a Pesquisa do Estado da Bahia-FAPESB).
Notes
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