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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

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MRP1 and its role in anticancer drug resistance

Jamie F Lu1, Deep Pokharel1, Mary Bebawy1

  • 1a Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney , Broadway , NSW , Australia.

Drug Metabolism Reviews
|November 7, 2015
PubMed

Insights

Multidrug resistance (MDR) in cancer involves ATP-binding cassette transporters like MRP1, which expel drugs. This review covers MRP1

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Multidrug resistance (MDR) in cancer is a significant clinical challenge.
  • Overexpression of ATP-binding cassette (ABC) transporter proteins, such as multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein, is a key mechanism of MDR.
  • MRP1 actively protects cells by effluxing a wide range of chemotherapy drugs, contributing to treatment failure.

Purpose of the Study:

  • To review the current understanding of MRP1, including its mechanisms, structure, substrates, and binding sites.
  • To discuss the clinical relevance of MRP1 in cancer multidrug resistance.
  • To highlight ongoing efforts in the development of MRP1 inhibitors and explore the role of microparticle-mediated intercellular transfer of the MRP1 phenotype.

Main Methods:

  • Literature review of recent research on MRP1.
  • Analysis of studies on MRP1 structure, function, and substrate interactions.
  • Examination of research on MRP1 inhibitors and microparticle-mediated drug resistance transfer.

Main Results:

  • Detailed elucidation of MRP1's mechanisms of action, structure, substrates, and binding sites.
  • Established clinical relevance of MRP1 in the context of cancer MDR.
  • Identified microparticles as a mechanism for rapid intercellular transfer of the MRP1 phenotype, with significant clinical and therapeutic implications.

Conclusions:

  • MRP1 is a critical factor in cancer multidrug resistance, necessitating targeted inhibition.
  • Understanding MRP1's function and inhibition is crucial for developing more effective cancer therapies.
  • The intercellular transfer of MRP1 via microparticles represents a novel therapeutic target for overcoming MDR.
Keywords:
MicroparticlesP-glycoproteincancerintercellular transfermultidrug resistancemultidrug resistance-associated protein 1trait dominance

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