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Modulators of P-glycoprotein-associated multidrug resistance

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Molecular and Clinical Advances in Anticancer Drug Resistance

Part of the book series: Cancer Treatment and Research ((CTAR,volume 57))

Abstract

Multidrug resistance associated with overexpression of P-glycoprotein (Pgp-MDR) is a well-documented experimental phenomenon whose pharmacologic, biochemical, and molecular basis is known. Its importance resides in the fact that it appears to have clinical correlates, so attempts to reverse or circumvent Pgp-MDR clearly assume high priority. There is a considerable body of experimental work showing that certain classes of membrane-active drugs are capable of circumventing MDR to varying degrees, but it remains to be seen whether these agents will be useful clinically. The goal in this chapter is to discuss the actions of these modulators. The general features of Pgp-MDR will be briefly outlined and its and differences from other forms of MDR recently described will be highlighted. The main focus will be on compounds that can modulate Pgp-MDR. Our current understanding of the mechanism(s) by which these agents work in MDR cells will be summarized, current models for modulator design will be discussed, and some of the ongoing clinical studies with these agents, as well as their attendant problems will be outlined. The conclusion offers some thoughts about future directions of modulator studies.

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  1. William T. Beck
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  1. Fox Chase Cancer Center, USA

    Robert F. Ozols

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Beck, W.T. (1991). Modulators of P-glycoprotein-associated multidrug resistance. In: Ozols, R.F. (eds) Molecular and Clinical Advances in Anticancer Drug Resistance. Cancer Treatment and Research, vol 57. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3872-1_7

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