Pharmacogenetics in Oncology: A Promising Field

Houtsma, D.; Guchelaar, H.J.; Gelderblom, H. (2010)

Article / Letter to editor

Pharmacogenetics is a rapidly developing field, especially in oncology. In the most ideal situation pharmacogenetics will allow oncologists to individualize therapy based on patients' individual germline genetic test results. This can help to improve efficacy, reduce toxicity and predict non-responders in a way that alternative therapy can be chosen or individual dose adjustments can be made. Multiple pathways have been studied extensively of which a brief review is presented here. Increased 5FU toxicity is associated with variations in the DPYD gene, TYMS gene and MTHFR gene. Furthermore variations in the UGT1A gene and the ABCB1 gene influence irinotecan metabolism and disposition. Other genetic changes result in reduced DNA repair capacity related to platinum efficacy or reduced cytochrome P450 2D6 activity related to tamoxifen efficacy. Despite the extensive number of pharmacogenetic studies and promising results, it is still unclear when and how pretreatment genetic screening should be implemented in oncology. Future prospective studies should focus on the effect of pharmacogenetics on patient outcome and combine this with cost effectiveness evaluations. Thus supplying us with predictive models helping in deciding when pretreatment genetic screening is useful.

• Pharmacogenetics pharmacogenomics single nucleotide polymorphism oncology thymidylate-synthase gene thiopurine s-methyltransferase colorectal-cancer patients acute lymphoblastic-leukemia dihydropyrimidine dehydrogenase gene fluoropyrimidine-based chemotherapy single nucleotide polymorphisms cell lung-cancer severe 5-fluorouracil-associated toxicity udp-glucuronosyltransferase gene

• All authors: Houtsma, D.; Guchelaar, H.J.; Gelderblom, H.
• Date: 2010-01-31
• Journal: Current Pharmaceutical Design
• Volume: 16
• Issue: 2
• Pages: 155 - 163
• DOI: doi:10.2174/138161210790112719