[Multiple drug resistance: a problem in cancer chemotherapy].

One of the main problems in clinical oncology is an acquired cellular drug resistance. Special attention deserves the multidrug resistance phenomenon (MDR) involving tumors which become resistant to a wide spectrum of non-related drugs to which they have never been exposed. Several mechanisms responsible for this phenomenon have been described. Among them is the increased expression of the MDR1 gene which encodes the plasma membrane glycoprotein P-gp. This glycoprotein is an energy-dependant multidrug efflux pump of wide specificity. It seems to have a normal physiological function but in some tumors resistant to chemotherapy its expression is increased. In cell lines the increased expression of P-gp is correlated with a decreased accumulation and retention of drugs inside the cells. In addition to P-gp, at least two other mechanisms of multidrug resistance have been described: a decreased expression and changes in the catalytic activity of topoisomerase II enzyme, and changes in glutathione transferase levels. Through biochemical and molecular methods researchers continue to look for a correlation between non-responding tumors and changes in the known drug-resistance mechanisms. These studies suggest that several factors are involved in the cellular drug resistance observed in human tumors, and probably are interacting between them. In clinical practice, the need of controlling MDR phenomena has led to the creation of alternate therapeutic strategies.