Cancer pharmacogenomics: current and future applications.
Heterogeneity in patient response to chemotherapy is consistently observed across patient populations. Pharmacogenomics is the study of inherited differences in interindividual drug disposition and effects, with the goal of selecting the optimal drug therapy and dosage for each patient. Pharmacogenomics is especially important for oncology, as severe systemic toxicity and unpredictable efficacy are hallmarks of cancer therapies. In addition, genetic polymorphisms in drug metabolizing enzymes and other molecules are responsible for much of the interindividual differences in the efficacy and toxicity of many chemotherapy agents. This review will discuss clinically relevant examples of gene polymorphisms that influence the outcome of cancer therapy, and whole-genome expression studies using microarray technology that have shown tremendous potential for benefiting cancer pharmacogenomics. The power and utility of the mouse as an experimental system for pharmacogenomic discovery will also be discussed in the context of cancer therapy.
Watters
James W
JW
Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave-Campus Box 8069, St Louis, MO 63110, USA.
McLeod
Howard L
HL
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP); D004195:Disease Models, Animal; D005472:Fluorouracil / Q000009:adverse effects / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D015122:Mercaptopurine / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010597:Pharmacogenetics / Q000639:trends*; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D000077146:Irinotecan; D015122:Mercaptopurine; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; D013940:Thymidylate Synthase; C022745:thiopurine methyltransferase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005472:Fluorouracil; D002166:Camptothecin