Using genetic variation to optimize cancer chemotherapy

The high level of interpatient variation in response to chemotherapy and the lack of objective tools to select chemotherapy regimens for a given tumor type have created a clinical problem. A possible solution may be pharmacogenetics: the study of inherited DNA polymorphisms that influence drug disposition and effects in order to individualize drug treatment. Because unpredictable efficacy and high levels of systemic toxicity are common in cancer chemotherapy, pharmacogenetics is particularly appealing to oncologists. Polymorphisms in drug metabolism, drug transport, drug target, and DNA repair genes have been implicated interpatient variability in response to many chemotherapy agents. This review will discuss recent clinically relevant examples of cancer pharmacogenetics and how genetic differences are helping to shape the future of individualized cancer chemotherapy.