Glutathione S-transferases: an overview in cancer research.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Although polygenic factors are involved in increased risk of cancer, the interindividual GST variability plays a central role in reduce cells exposure to carcinogens.
Di Pietro
Giuliano
G
Universidade Estadual de Santa Cruz, Departamento de Ciências da Saúde, Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Ilhéus, Bahia 45662-900, Brazil. dipietrobr@yahoo.com.br
Magno
Luiz Alexandre V
LA
Rios-Santos
Fabrício
F
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors
D000970:Antineoplastic Agents; D011355:Prodrugs; D005982:Glutathione Transferase