Pharmacogenetics in oncology

Danesi, Romano and Di Paolo, Antonello and Bocci, Guido and Crea, Francesco and Del Tacca, Mario (2008) Pharmacogenetics in oncology. European Journal of Cancer Supplements, 6/2008 (14). pp. 74-78. ISSN 1359-6349

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Abstract

SUMMARY The number of studies reporting a relationship between DNA sequence variants and cancer treatment outcome are increasing in number. In particular, the following associations were found: dihydropyrimidine dehydrogenase (DPD) gene mutations and severe 5-FU toxicity, epidermal growth factor receptor mutations (EGFR) and responsiveness of NSCLC to gefitinib, ERCC1 polymorphisms and activity of cisplatin, genetic variants of UGT1A1 gene and severe neutropenia by irinotecan, thymidylate synthase (TS) gene polymorphisms and 5-FU sensitivity, and cytidine deaminase (CDA) genotype and expression of equilibrative nucleoside transporter-1 (hENT1) and response to gemcitabine. The next step in pharmacogenetic research should be the validation of these findings in randomized prospective trials, specifically designed to compare the outcome of treatment selected on the basis of patient’s genotype vs. standard approach. In conclusion, the improvement in genotyping technologies, combined with efficient and cost-effective analytical methods, may fulfill the promise of personalizing the treatment offered to cancer patients.

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