Pharmacogenetics and cancer chemotherapy.
Cancer chemotherapy is limited by significant inter-individual variations in responses and toxicities. Such variations are often due to genetic alterations in drug metabolising enzymes (pharmacokinetic polymorphisms) or receptor expression (pharmacodynamic polymorphisms). Pharmacogenetic screening prior to anticancer drug administration may lead to identification of specific populations predisposed to drug toxicity or poor drug responses. The role of polymorphisms in specific enzymes, such as thiopurine S-methyltransferases (TPMT), dihydropyrimidine dehydrogenase (DPD), aldehyde dehydrogenases (ALDH), glutathione S-transferases (GST), uridine diphosphate glucuronosyl-transferases (UGTs) and cytochrome P450 (CYP 450) enzymes in cancer therapy are discussed in this review.
Iyer
L
L
Committee on Clinical Pharmacology, University of Chicago, Illinois 60637, USA.
Ratain
M J
MJ
D000123:Acetyltransferases / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP); D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D010088:Oxidoreductases / Q000378:metabolism; D014530:Uridine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism
D000970:Antineoplastic Agents; D004798:Enzymes; D014530:Uridine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D000444:Aldehyde Dehydrogenase; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D000123:Acetyltransferases; D005982:Glutathione Transferase