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Updated: Sep 2, 2026

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

Modulation of multidrug resistance: a paradigm for translational clinical research

B I Sikic1

  • 1Stanford University School of Medicine, California, USA.

Oncology (Williston Park, N.Y.)
|June 17, 1999
PubMed

Insights

Cancer cells resist chemotherapy primarily through multidrug resistance (MDR), mediated by P-glycoprotein (P-gp). New drugs targeting P-gp and other resistance mechanisms offer promising strategies to improve cancer treatment outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cancer cell resistance is a primary obstacle to effective chemotherapy.
  • Multidrug resistance (MDR), driven by P-glycoprotein (P-gp) encoded by the MDR1 gene, is a well-characterized resistance mechanism.
  • Developing strategies to overcome MDR is crucial for enhancing chemotherapeutic success.

Purpose of the Study:

  • To review current understanding of MDR and P-gp.
  • To discuss novel P-gp inhibitors and other resistance modulators.
  • To explore the potential of combining MDR modulators with chemotherapy.

Main Methods:

  • Literature review of studies on MDR, P-gp, and resistance modulators.
  • Analysis of clinical trial data for P-gp inhibitors like valspodar.
  • Discussion of emerging agents targeting various resistance pathways.

Main Results:

  • Valspodar (PSC 833) is a key P-gp inhibitor in clinical development.
  • Concurrent inhibition of multiple resistance mechanisms shows promise.
  • Combination therapy may improve drug bioavailability and allow for oral administration.

Conclusions:

  • Targeting P-gp and other resistance mechanisms is a viable strategy to overcome chemotherapy resistance.
  • Combination therapies hold potential for enhanced efficacy, convenience, and reduced toxicity.
  • Further research and clinical trials are needed to optimize these approaches.

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