Glutathione S-transferase polymorphisms: cancer incidence and therapy.

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.