Pharmacogenetics of cancer chemotherapy.
Significant heterogeneity in the efficacy and toxicity of chemotherapeutic agents is observed within cancer populations. Pharmacogenetics (PGx) is the study of inheritance in interindividual variation in drug disposition. The allure of pharmacogenetics, in the treatment of cancer patients, comes from the potential for individualisation of cancer therapy, minimizing toxicity, while maximizing efficacy. In this review we will focus on the current and potential clinical applications of pharmacogenetics in cancer therapy by citing relevant examples and discussing the possible approaches which may be used to establish a reliable, reproducible and cost-effective test for clinically relevant genetic polymorphisms, using easily accessible biological samples (e.g., blood and tumour samples). Ideally, routine management of patients would include analysis of their single nucleotide polymorphism linkage disequilibrium (SNP-LD) profile prior to treatment, allowing stratification of patients into treatment groups, thus individualising their therapy. In order to achieve this ambition, a combination of different approaches (candidate gene, genome-wide and pathway driven) will be required from scientists and clinician scientists, as well as an increased understanding and incorporation of pharmacogenetic aims and endpoints into current and future clinical trials.
Abraham
Jean
J
Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Hills Road, Cambridge CB2 2XZ, UK. jean@abrahamblake.fsnet.co.uk
Earl
Helena M
HM
Pharoah
Paul D
PD
Caldas
Carlos
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004260:DNA Repair; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D002352:Carrier Proteins; D004798:Enzymes; D004247:DNA