Pharmacogenomics of Sex Difference in Chemotherapeutic Toxicity

Jeffrey Wang; Ying Huang

Abstract

Except for few cases, chemotherapeutic toxicity is in general influenced by multiple genetic factors and nongenetic factors including age, sex and drug-drug interactions. The manifestations of adverse drug reactions differ between men and women. In particular, women experience greater toxicity from certain chemotherapeutic drugs than men. Sexrelated factors are likely to play an increasing role in drug development and therapeutic decision-making in the future. The sex-selective toxicity could be attributed to sex-related differences in pharmacokinetic and pharmacodynamic properties of these drugs. Systematic pharmacogenomic investigation into sex difference in chemotherapeutic toxicity potentially presents an opportunity to assess the effects of multiple genetic factors or gene networks on sex-related differences in the toxicity of anti-cancer drugs. A thorough understanding of the interactions between sex, drug and gene will provide valuable insights in assessing the susceptibility of an individual to chemotherapy-induced toxicity, predicting the sex-related effects for any anticancer drug and ultimately achieving the goal of personalized cancer therapy.

Keywords: Sex difference, pharmacogenomics, chemotherapeutic toxicity, personalized drug therapy