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Updated: May 25, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Tyrosine kinase inhibitors as modulators of ABC transporter-mediated drug resistance

Suneet Shukla1, Zhe-Sheng Chen, Suresh V Ambudkar

  • 1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|February 14, 2012
PubMed

Insights

Tyrosine kinase inhibitors (TKIs) show promise in cancer treatment but can be affected by ATP-binding cassette (ABC) transporters. Understanding TKI-ABC transporter interactions is crucial for overcoming drug resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Tyrosine kinases (TKs) regulate critical cellular processes including proliferation, apoptosis, and angiogenesis, and their dysregulation is linked to various cancers.
  • Tyrosine kinase inhibitors (TKIs) represent a targeted therapy approach, with several approved for clinical use or in trials.
  • TKIs, while effective, are substrates for ATP-binding cassette (ABC) transporters, impacting their pharmacokinetics and efficacy.

Purpose of the Study:

  • To review recent findings on the interactions between clinically significant TKIs and ABC drug transporters.
  • To highlight the role of ABC transporters in TKI resistance and altered pharmacokinetics.
  • To inform future TKI development by considering transporter-mediated resistance mechanisms.

Main Methods:

  • Literature review of recent studies on TKI-ABC transporter interactions.
  • Analysis of data on the impact of ABC transporters on TKI pharmacokinetics and resistance.
  • Synthesis of current knowledge regarding clinically relevant TKIs and their transporter interactions.

Main Results:

  • TKIs are substrates for ABC transporters, leading to efflux from cells and reduced intracellular drug concentrations.
  • ABC transporter activity is a significant factor in the development of resistance to TKI therapy in cancer patients.
  • Variations in ABC transporter expression and function influence TKI efficacy and patient response.

Conclusions:

  • Interactions between TKIs and ABC transporters are a key determinant of therapeutic outcomes and drug resistance.
  • Future development of novel TKIs should strategically address and overcome ABC transporter-mediated resistance.
  • Targeting or circumventing ABC transporters may enhance the effectiveness of TKI-based cancer therapies.

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