Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response.
Tamoxifen continues to be a standard endocrine therapy for the prevention and treatment of estrogen receptor (ER)-positive breast cancer. Tamoxifen can be considered a classic "pro-drug," requiring metabolic activation to elicit pharmacological activity. CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. The a priori knowledge of the pharmacogenetic variation known to abrogate CYP2D6 enzyme activity may provide a means by which the hormonal therapy of breast cancer can be individualized.
Goetz
M P
MP
Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. goetz.matthew@mayo.edu
Kamal
A
A
Ames
M M
MM
D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D013629:Tamoxifen / Q000378:metabolism* / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6