[Pharmacogenetics and pharmacogenomics of cancers].
Sequencing the human genome brings new tools for the individualisation of cancer chemotherapy, firstly thanks to the identification of polymorphisms of genes involved in anticancer drug metabolism or activity (Pharmacogenetics), and secondly thanks to the determination of tumour gene expression profiles and their relationship to chemosensitivity and chemoresistance (Pharmacogenomics). A few functional polymorphisms have been known for a long time (thiopurine methyltransferase, glutathion S-transferases), but several new ones have been identified recently, at the level of the genes encoding drug targets (thymidylate synthase), at the level of DNA repair enzymes (XPD) or at the level of transport proteins (MDR1). On the other hand, the research of correlations between gene expression profiles and chemosensitivity has been performed on the in vitro models of the National Cancer Institute and may allow crucial improvements in the identification of patients who would best take advantage of a specific chemotherapy. Clinical trials, first on a retrospective basis, then on a prospective one, are implemented to validate this approach.
Robert
J
J
Institut Bergonié et université Victor-Segalen, 229, cours de l'Argonne, 33076 Bordeaux, France. robert@bergonie.org
D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*