MULTIDRUG-RESISTANCE - FROM BENCH TO THE BEDSIDE

Multifactorial resistance is the main mechanism of chemotherapy failur e in cancers. Multidrug resistance (MDR) is related to the expression of a 170 kDa membrane glycoprotein, the so-called P-glycoprotein (P-gp ). This protein is able to extrude drugs of various structures and mec hanisms out of the cytoplasm. P-gp is a pronostic value in hemopathy a s well as in child sarcoma, osteosarcoma and neuroblastoma. Modulator agents of different generations are capable of inhibiting P-gp. MDR mo dulation is obtained in hemopathies and is associated with an eradicat ion of the P-gp (+) cell clones. In solid tumors, clinical trials usin g verapamil or cyclosporin are not so convincing. It is likely that ot her mechanisms of resistance are responsible for tumor progression, su ch as the MRP system glutathion and topoisomerases. A better knowledge of multifactorial resistance and drug synthesis counteracting these r esistance mechanisms will allow to elaborate new therapeutic basis for cancer therapy.