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Updated: Jul 16, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters

Andaleeb Sajid1, Hadiar Rahman1, Suresh V Ambudkar2

  • 1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Nature Reviews. Cancer
|September 15, 2023
PubMed

Insights

Multidrug resistance in cancer is often caused by ATP-binding cassette (ABC) transporters like ABCB1, ABCG2, and ABCC1. Understanding their structure and function offers new strategies to improve chemotherapy effectiveness.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Pharmacology

Background:

  • Cancer cells develop resistance to chemotherapy drugs, limiting treatment efficacy.
  • Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCG2, and ABCC1, is a primary mechanism for multidrug resistance.
  • These transporters efflux anticancer drugs, reducing their intracellular concentration and therapeutic effect.

Purpose of the Study:

  • To review recent advancements (past 5 years) in understanding ABCB1, ABCG2, and ABCC1 transporters.
  • To explore the molecular basis of their broad substrate specificity.
  • To discuss novel therapeutic strategies for overcoming ABC transporter-mediated chemoresistance.

Main Methods:

  • Analysis of high-resolution structural data.
  • Biophysical studies of transporter function.
  • In silico modeling and simulations.
  • Review of emerging therapeutic approaches.

Main Results:

  • Significant progress in elucidating the structural basis for the broad substrate specificity of ABCB1, ABCG2, and ABCC1.
  • Identification of novel strategies to inhibit ABC transporter function.
  • Exploration of genetic modification techniques like CRISPR-Cas9 and protein re-engineering.

Conclusions:

  • Integrating structural and mechanistic insights of ABC transporters into clinical trials can enhance chemotherapy efficacy.
  • Targeting ABC transporters offers a promising avenue to combat multidrug resistance in cancer.
  • Future research should focus on translating these findings into improved patient outcomes.

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