Pharmacogenomic applications in oncology.
Oncology chemotherapeutics frequently exhibit a narrow therapeutic index, further complicated by the serious nature of dosing either too high (dangerous toxicities) or too low (loss of antitumor benefits). This underscores the need for optimal individualized drug selection and dosing, especially with agents that have wide interpatient variability. Pharmacogenomic assessment of drug metabolizing enzymes can improve the ability to optimally dose patients being treated with certain agents such as 6-mercaptopurine, irinotecan, tamoxifen, and flurouracil. Two of these agents (6-mercaptopurine and irinotecan) already have mention of pharmacogenomic testing in their FDA approved package inserts. Ongoing retrospective and prospective trials will help to further optimize the place in clinical practice for not only performing these pharmacogenomic assessments but, more importantly, how the results should be incorporated into therapy dosing decisions for patients.
UNC School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, Chapel Hill, NC 27599-7569, USA. cwalko@email.unc.edu
Christine M
CM
Walko
Ogechi
O
Ikediobi
D000970:Antineoplastic Agents / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008495:Medical Oncology; D008780:Methyltransferases / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000187:drug effects*; D011446:Prospective Studies; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D019389:Cytochrome P-450 CYP2D6; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D014453:Glucuronosyltransferase