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Review

Nature Reviews Cancer 3, 912–920 (1 December 2003) | doi:10.1038/nrc1233

Cancer pharmacogenetics: polymorphisms, pathways and beyond

Cornelia M. Ulrich , Kim Robien & Howard L. McLeod

Inherited genetic variations can affect a patient's response to chemotherapeutic agents given for cancer. Pharmacogenetics aims to use knowledge of these variations to 'tailor' therapy for improved response and reduced toxicity. Most research so far has focused on single polymorphisms. A more comprehensive approach to predict treatment response will be to consider genetic variation in entire biological and pharmacological pathways. Of particular relevance to cancer chemotherapy is folate metabolism, which is the target of methotrexate and 5-fluorouracil. Furthermore, efforts have begun to construct pathways of genes that have pharmacological relevance for individual chemotherapeutic agents. Together, these pathway strategies offer a higher likelihood of achieving the promise of genetically guided cancer therapy.