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