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Pharmacogenomics of tamoxifen and irinotecan therapies

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

  • 1Division 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.

Clinics in Laboratory Medicine
|December 9, 2008
PubMed

Insights

Genetic variations in drug-metabolizing enzymes impact cancer drug effectiveness. Genotyping uridine diphosphate-glucuronyltransferase 1A1 (UGT1A1) and cytochrome P450 (CYP) 2D6 can guide irinotecan and tamoxifen therapy, but more research is needed.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Drug Metabolism

Background:

  • Genetic variability in drug-metabolizing enzymes influences chemotherapy efficacy and toxicity.
  • Polymorphisms in uridine diphosphate-glucuronyltransferase 1A1 (UGT1A1) and cytochrome P450 (CYP) 2D6 are linked to irinotecan and tamoxifen response.
  • Genotyping for UGT1A1 and CYP2D6 is increasingly recommended for patients receiving these chemotherapeutics.

Purpose of the Study:

  • To review the current utility of UGT1A1 and CYP2D6 genotyping in cancer chemotherapy.
  • To highlight the clinical relevance of genetic variations in drug metabolism for irinotecan and tamoxifen.
  • To identify areas requiring further investigation in pharmacogenetic applications.

Main Methods:

  • Literature review of studies on UGT1A1 and CYP2D6 polymorphisms and their clinical impact.
  • Analysis of the correlation between genetic variations and patient response to irinotecan and tamoxifen.
  • Synthesis of current knowledge on the role of genotyping in cancer treatment.

Main Results:

  • Reduced UGT1A1 activity is associated with irinotecan toxicity in colorectal cancer patients.
  • Reduced CYP2D6 activity can lead to tamoxifen treatment failure due to impaired conversion to active metabolites.
  • Genotyping provides insights into individual drug metabolism, influencing treatment decisions.

Conclusions:

  • UGT1A1 and CYP2D6 genotyping show promise in optimizing cancer chemotherapy.
  • Further studies are necessary to fully elucidate the clinical utility and address remaining questions regarding these pharmacogenetic tests.
  • Personalized medicine approaches incorporating genetic information can improve patient outcomes in cancer treatment.

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