Irinotecan pharmacogenomics.
Irinotecan is a camptothecin analog used as an anticancer drug. Severe, potentially life-threatening toxicities can occur from irinotecan treatment. Although multiple genes may play a role in irinotecan activity, the majority of evidence to date suggests that variation in expression of UGT1A1 caused by a common promoter polymorphism (UGT1A1*28) is strongly associated with toxicity; however, this link is dose dependent. Variations in other pharmacokinetic genes, particularly the transporter ABCC2, also contribute to irinotecan toxicity. In addition, recent studies have shown that pharmacodynamic genes such as TDP1 and XRCC1 can also play a role in both toxicity and response.
Marsh
Sharon
S
UNC Institute for Pharmacogenomics & Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. smarsh@pharmacy.ualberta.ca
Hoskins
Janelle M
JM
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D000089762:Multidrug Resistance-Associated Protein 2; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000089762:Multidrug Resistance-Associated Protein 2; D000099148:UGT1A1 Enzyme; C000715087:ABCC2 protein, human