The role of drug-metabolising enzymes in clinical responses to chemotherapy.
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 patient's response to a particular chemotherapy agent based on knowledge of their genetic composition through in vivo phenotyping of drug-metabolising enzymes.
Scripture
Charity D
CD
National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA.
Figg
William D
WD
Sparreboom
Alex
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000502:physiology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System