Pharmacogenomics of tamoxifen and irinotecan therapies

Alicia Algeciras-Schimnich; Dennis J O'Kane; Christine L H Snozek

doi:10.1016/j.cll.2008.05.004

Pharmacogenomics of tamoxifen and irinotecan therapies

Clin Lab Med. 2008 Dec;28(4):553-67. doi: 10.1016/j.cll.2008.05.004.

Authors

Alicia Algeciras-Schimnich¹, Dennis J O'Kane, Christine L H Snozek

Affiliation

¹ 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.

PMID: 19059062
DOI: 10.1016/j.cll.2008.05.004

Abstract

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.

Publication types

Review

MeSH terms

Antineoplastic Agents, Hormonal / administration & dosage
Antineoplastic Agents, Hormonal / pharmacokinetics
Antineoplastic Agents, Hormonal / therapeutic use*
Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Agents, Phytogenic / pharmacokinetics
Antineoplastic Agents, Phytogenic / therapeutic use*
Breast Neoplasms / drug therapy
Breast Neoplasms / enzymology
Breast Neoplasms / genetics
Camptothecin / administration & dosage
Camptothecin / analogs & derivatives*
Camptothecin / pharmacokinetics
Camptothecin / therapeutic use
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / enzymology
Colorectal Neoplasms / genetics
Cytochrome P-450 CYP2D6 / genetics*
Female
Genotype
Glucuronosyltransferase / genetics*
Humans
Irinotecan
Pharmacogenetics
Polymorphism, Genetic
Tamoxifen / administration & dosage
Tamoxifen / pharmacokinetics
Tamoxifen / therapeutic use*
Treatment Outcome

Substances

Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Tamoxifen
Irinotecan
Cytochrome P-450 CYP2D6
UGT1A1 enzyme
Glucuronosyltransferase
Camptothecin