Pharmacogenetics and Cancer Treatment in Children

Abstract

Despite significant improvements in the treatment of childhood cancer over the past several decades, there remains a need for improved cure rates for many tumour types. It is therefore essential that, in addition to the development of novel anticancer drugs, selected on the basis of the molecular and cellular pathology of the target tumour, we continue to explore more effective ways of using conventional chemotherapeutics. Improved knowledge of the clinical pharmacology of an increasing number of chemotherapeutics may facilitate their efficacious use with minimal toxicity and a decreased likelihood of other unwanted long-term effects. In this respect, it is important to consider the many cases where variations in pharmacokinetics may reflect genetic polymorphisms in enzymes involved in drug metabolism and transport. In the same way that inter-patient pharmacokinetic variation has been used successfully to facilitate individualisation of dosing for a number of anticancer drugs, the more recent appeal of pharmacogenetics research has significant potential for improving the clinical treatment of children with cancer. Indeed, pharmacogenetic approaches may allow for the upfront selection of which drugs are likely to be most beneficial, in addition to defining the most appropriate dosing regimens for individual patients. This chapter highlights a number of polymorphisms in genes, which play important roles in determining anticancer drug disposition and response or toxicity in a paediatric oncology setting.