Interpatient Variability in Response to Drugs and Toxicity

The main prognostic factors in cancer are age, tumor size, stage of disease, histologic type of the tumor, pathological grade, and in some cases hormone-receptor status. There are suggestions that the same genes that are implicated in cancer risk may also be involved in a person's propensity to carcinogenic exposure and/or to modulation of therapeutic outcome (1). Therefore, constructing genetic profiles that can be used to individualize therapy may also increase our understanding of cancer risk genes and may be applied to cancer development and prediction of outcome.

A large number of genes are likely to influence the response of a tumor to an individual chemotherapeutic agent. However, studying the genetic contribution to chemosen-sitivity in the clinic is challenging because drug responses reflect not only properties intrinsic to the target cell but also host metabolic properties. Candidate gene approaches have had some success in identifying genes important in response to chemotherapy used to treat cancer; however, there has been limited success in identifying genetic factors that predict patients at risk for chemotherapeutic induced toxicities (2). The focus of this chapter is to describe the use of classical genetic approaches in the context of identifying genes important in response/toxicities associated with chemotherapy.

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