Clinical effects of multidrug resistance in neoplasms

Abstract

Resistance to chemotherapy remains a major cause of the systemic anti-cancer treatment failure. The best known mechanism is often attributed to the function of drug transporter proteins in the plasma membrane, which actively remove drugs from neoplastic cells. Abnormal overexpression of these proteins is the most frequently described factor connected with cytostatics resistance.
Among cellular transporter proteins the most important role plays glicoprotein P (Pgp). Increased level of this protein is considered as a poor prognostic factor both, in leukaemias and in many solid tumors. Clinical significance of other multidrug resistance proteins (MRP1, BCRP and LRP) remains subject of intensive studies.
In experimental models and clinical trials different strategies are used to limit Pgp expression. Introduction of the second and third generation of Pgp blockers is a source of hope for the reversion of multidrug resistance, especially in lymphoid and blood neoplastic disorders.