Cyclosporin A and analogues as multidrug resistance modulating agents in tumour cell

Abstract

Multidrug resistance (MDR) to chemotherapy is one of the major obstacles in the treatment of cancer patients. The resistance process is multifactorial but the best characterized mechanism involved is the overexpression of Pglycoprotein (Pgp), a plasma membrane protein that functions as an efflux pump leading to a decreased intracellular drug concentration. Circumvention of MDR can be obtained using reversing agents capable of inhibiting the activity of Pgp and other drug efflux pumps. In the present review the use of the immunosupresive agent Cyclosporin A and its analogues as reversing agents is discussed. Aspects such as their combination to cyclophilins, their ability to modify Pgp functional activity and their clinical use, especially in leukemias, are discussed based on the literature and on the authors results.