MULTIDRUG-RESISTANCE DUE TO P-GLYCOPROTEIN

Multi-drug resistance (MDR) is due to the presence in neoplastic cells of the transmembrane glycoprotein P-170. The P-170 increases drug efflux by combining with the drug and adenosine triphosphate. This energy dependent drug efflux may be reversed by agents, e.g. verapamil, which compete with drugs for receptors on the plasma membrane. High expression of P-170 is associated with reduced sensitivity to MDR-associated cytotoxic drugs, e.g. doxorubicin in vitro by renal and breast carcinoma cells. Verapamil has been most effective in increasing the effect of chemotherapy in patients with multiple myeloma. In contrast, negative results have been reported for 'solid' tumours such as carcinoma of the colon and kidney.