The role of drug-metabolising enzymes in clinical responses to chemotherapy

Abstract

Interindividual differences in efficacy and toxicity of cancer chemotherapy are especially important given the narrow therapeutic index of these drugs. Pharmacokinetic and pharmacodynamic responses to chemotherapy are difficult to predict in a particular patient as numerous variables (e.g., age, gender, concomitant medications and concomitant illness) can alter drug responses. Inherited variations in genes involved in drug metabolism have also been shown to contribute to altered responses to cancer treatment. There are several clinically relevant examples of genetic polymorphisms in drug-metabolising enzymes that alter outcomes of patients treated with chemotherapy agents. It may be possible to predict a patients response to a particular chemotherapy agent based on knowledge of their genetic composition through invivo phenotyping of drug-metabolising enzymes.

Keywords::

• cancer chemotherapy
• cytochrome P450
• genotype
• interindividual variability
• pharmacogenomics

Acknowledgements

This work was supported by the Intramural Research Programme of the National Cancer Institute. This is a US Government work. There are no restrictions on its use. The views expressed within this paper do not necessarily reflect those of the US Government.