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Townsend D , Tew K
Cancer drugs, genetic variation and the glutathione-S-transferase gene family
Am J Pharmacogenomics. 2003 ;3(3) :157-72
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The glutathione-S-transferase (GST) super family comprises multiple isozymes (Alpha, Mu, Pi, Omega, Theta, and Zeta) with compelling evidence of functional polymorphic variation. Over the last two decades, a significant body of data has accumulated linking aberrant expression of GST isozymes with the development and expression of resistance to cancer drugs. Clinical correlation studies show that genetic differences within the human GST isozymes may play a role in cancer susceptibility and treatment. The initial confusion was presented by the fact that not all drugs used to select for resistance were substrates for thioether bond catalysis by GSTs. However, recent evidence that certain GST isozymes possess the capacity to regulate mitogen activated protein kinases presents an alternative explanation. This dual functionality has contributed to the recent efforts to target GSTs with novel small molecule therapeutics. While the ultimate success of these attempts remains to be shown, at least one drug is in late-stage clinical testing. In addition, the concept of designing new drugs that might interfere with protein:protein interactions between GSTs and regulatory kinases provides a novel approach to identify new targets in the search for cancer therapeutics.
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