DRUG-RESISTANCE GENES

Among the different mechanisms of multidrug resistance, the overexpression of the mdr1 gene has been actively investigated during the last 5 years. This gene encodes a 170 kDa protein, named P-gp, a member of a transporter superfamily, the ABC (ATP Binding Cassette) proteins. P-gp actively expels out of the tumoral cell different drugs like anthracyclins, vinca alkaloids, epipodophyllotoxins. The involvement of mdr1 gene in clinical drug resistance is now demonstrated, and several trials using P-gp modulators and chemotherapy are going on in resisting tumors. Other intrinsic drug resistance mechanisms, such as increase of intracellular glutathion content or decrease of topoisomerase activity, could be involved in clinical drug resistance.