CYTOTOXIC AND CYTOSTATIC EFFECTS OF ANTITUMOR AGENTS INDUCED AT THE PLASMA-MEMBRANE LEVEL

A variety of antitumor agents inhibit cell proliferation by interacting with the plasma membrane. They act as growth factor antagonists, growth factor receptor blockers, interfere with mitogenic signal transduction or exert direct cytotoxic effects. The P-glycoprotein encoded by the MDR1 gene represents a transmembrane protein which catalyzes the efflux of various antitumor agents. This membrane protein is the target of compounds acting as Multi-Drug Resistance (MDR)-modulators. Finally, several established antitumor agents which are considered to represent DNA-targeted drugs, including anthracyclines, platinum complexes and alkylating agents, cause a variety of membrane lesions. Their contribution to the antitumor activity of these drugs is discussed.