Germline genomics and predisposition to serious adverse drug reactions with anti-cancer drugs

Munir Pirmohamed1

1University of Liverpool, Liverpool, UK

Abstract

The benefit-risk profile of drugs is important in every disease area including cancer. As cancer therapy becomes more effective, it is important to understand the mechanisms behind serious adverse drug reactions associated with anti-cancer drugs in order to further improve the benefit-risk ratio, and reduce cancer survivor issues. Using the germline genome to identify predisposing factors for adverse drug reactions has seen major advances in non-cancer areas, but perhaps less so in cancer. The identification of a genetic predisposing factor for an adverse drug reaction may have several benefits: (a) a better understanding of the mechanism of toxicity, which may allow the development of interventional agents, but will also feed into future drug development; and (b) the development of predictive testing which could then be used prior to drug prescription to optimise both the choice and dose of drug. Both these scenarios require the identification and recruitment of deeply phenotyped patients, a major limitation at present. For predictive testing, a validated genetic test is required together with an appropriate interventional strategy to reduce harm (increased monitoring, alteration of dose or different drug choice). These areas will be considered in the talk focusing on anti-cancer drugs, but comparing and contrasting with non-cancer therapeutic areas.