ANTICANCER DRUG-RESISTANCE

Due to inefficacy of chemotherapy in several cancers, chemoresistance mechanisms which are intrinsic to tumor cells have been extensively de scribed in human cancer cell lines, Detoxifying mechanisms including a ctive efflux pumps (P-gp, MRP or LRP) and/or drug inactivation (glutat hione) as well as increased DNA repair have been identified and demons trated to be involved in chemoresistance processes, Moreover expressio n of genes implicated in proliferation, differentiation or apopotosis functions has been shown to indicate drug response, Several mechanisms very often coexist within the tumor cell: it is possible even that de toxifying mechanisms are dependent on oncogenes and suppressor genes r egulating proliferation, differentiation and/or apoptosis, In human tu mor specimens, some of these mechanisms are regularly found and thus l ead to develop strategies to block them, In that respect, the first ex ample is the development of modulators of P-gP, a membrane efflux prot ein, which constitutes the archetype of detoxifying drug mechanisms, I n 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.