Glutathione and glutathione-dependent enzymes in cancer drug resistance

Genetic and biochemical evidence has demonstrated that glutathione and glut athione-dependent enzymes play a central role in cellular defence against t oxic environmental agents. Modulation of cellular glutathione homeostasis c an also have a profound effect on the sensitivity of cancer cells to a wide range of drugs used in chemotherapy. These effects are produced by multifa ctorial mechanisms that involve inactivation of toxic electrophiles by conj ugation, modulation of cellular redox state, activation of drug transporter systems and regulation of cell signalling and repair pathways. New data de monstrating the importance of these pathways in cytoprotection and greater understanding of the mechanisms which regulate their function reveal a numb er of new targets for novel anti-cancer agents. It is critical, however, if these targets are to be exploited correctly that the dynamics of glutathio ne regulation are taken into account.