Pharmacogenomics of tamoxifen and irinotecan therapies.
Genetic variability in drugmetabolizing enzymes affects the toxicity and efficacy of many compounds, including the chemotherapeutic agents irinotecan and tamoxifen. The correlation of clinical response to polymorphisms in enzymes associated with metabolism of these two drugs has led to the recommendation that patients who receive them undergo genotyping analysis. Irinotecan toxicity in patients who have colorectal cancer has been linked to reduced activity of uridine diphosphate-glucuronyltransferase 1A1 (UGT1A1). Reduced cytochrome P450 (CYP) 2D6 activity leads to therapeutic failure of tamoxifen in the prevention and treatment of breast cancer, as a result of absence of conversion of the prodrug to its active forms. This article discusses current knowledge of the usefulness of UGT1A1 and CYP2D6 genotyping in the context of cancer chemotherapy and highlights the need for additional studies to clarify the many issues remaining.
Algeciras-Schimnich
Alicia
A
Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, College of Medicine, Hilton 730, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
O'Kane
Dennis J
DJ
Snozek
Christine L H
CL
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013629:Tamoxifen / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D019389:Cytochrome P-450 CYP2D6; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D013629:Tamoxifen; D000099148:UGT1A1 Enzyme