MODULATORS OF MULTIDRUG-RESISTANCE - PRECLINICAL STUDIES

Numerous compounds have been identified that sensitize multidrug-resistant cells to chemotherapeutic drugs in experimental systems. The mechanism of activity of these pharmacologic agents, termed chemosensitizers, appears to be mediated through direct inhibition of the drug efflux activity of the MDR1 gene product, P-glycoprotein. This article describes commonly used experimental models for the discovery and preclinical evaluation of new chemosensitizers, reviews those agents that possess potential for clinical use to circumvent multidrug resistance in humans, and discusses strategies to identify novel drugs of this type with improved efficacy and reduced toxicity.