[Resistance to anticancer drugs].
Due to inefficacy of chemotherapy in several cancers, chemoresistance mechanisms which are intrinsic to tumor cells have been extensively described in human cancer cell lines. Detoxifying mechanisms including active efflux pumps (P-gp, MRP or LRP) and/or drug inactivation (glutathione) as well as increased DNA repair have been identified and demonstrated to be involved in chemoresistance processes. Moreover expression of genes implicated in proliferation, differentiation or apoptosis functions has been shown to indicate drug response. Several mechanisms very often coexist within the tumor cell: it is possible even that detoxifying mechanisms are dependent on oncogenes and suppressor genes regulating proliferation, differentiation and/or apoptosis. In human tumor specimens, some of these mechanisms are regularly found and thus lead to develop strategies to block them. In that respect, the first example is the development of modulators of P-gP, a membrane efflux protein, which constitutes the archetype of detoxifying drug mechanisms. In spite of technical difficulties encountered to properly identify and quantify expressions of these biomarkers, ongoing research in cancer chemotherapy now largely relies on chemoresistance mechanisms.
Bénard
J
J
Laboratoire de Pharmacologie clinique et moléculaire, Institut Gustave Roussy, Villejuif.
Rixe
O
O
D004260:DNA Repair; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology*; D005544:Forecasting; D006801:Humans; D010641:Phenotype
Résistance aux drogues anticancéreuses.