Is Resistance Useless? Multidrug Resistance and Collateral Sensitivity

Overview

Journal Trends Pharmacol Sci

Specialty Pharmacology

Date 2009 Sep 19

PMID 19762091

Citations 103

Authors

Matthew D Hall

Misty D Handley

Michael M Gottesman

Affiliations

Soon will be listed here.

Abstract

When cancer cells develop resistance to chemotherapeutics, it is frequently conferred by the ATP-dependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P-gp can efflux a wide range of cancer drugs; its expression confers cross-resistance, termed "multidrug resistance" (MDR), to a wide range of drugs. Strategies to overcome this resistance have been actively sought for more than 30 years, yet clinical solutions do not exist. A less understood aspect of MDR is the hypersensitivity of resistant cancer cells to other drugs, a phenomenon known as "collateral sensitivity" (CS). This review highlights the extent of this effect for the first time, and discusses hypotheses (e.g. generation of reactive oxygen species) to account for the underlying generality of this phenomenon, and proposes exploitation of CS as a strategy to improve response to chemotherapy.

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