Molecular mechanisms of drug resistance in tyrosine kinases cAbl and cKit

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Updated: Jun 2, 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

Jonathan P DiNitto1, Joe C Wu

  • 1Infinity Pharmaceuticals, Cambridge, MA, USA.

Critical Reviews in Biochemistry and Molecular Biology
|May 5, 2011
PubMed

Insights

Protein kinase inhibitors are vital cancer treatments, but acquired resistance limits their effectiveness. This review details common resistance mechanisms and strategies to overcome them.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Protein kinase inhibitors are a cornerstone of modern cancer therapy.
  • Acquired resistance to these drugs diminishes therapeutic efficacy over time.
  • Understanding resistance mechanisms is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To review common molecular mechanisms of acquired resistance to kinase inhibitors.
  • To highlight resistance in cAbl and cKit kinases.
  • To discuss strategies for overcoming drug resistance in cancer therapy.

Main Methods:

  • Biochemical approaches
  • Kinetic analyses
  • Structural studies
  • Literature review

Main Results:

  • Identified common molecular mechanisms underlying acquired resistance to kinase inhibitors.
  • Detailed resistance in cellular form of Abelson leukemia virus tyrosine kinase (cAbl) and cKit.
  • Highlighted a novel mechanism involving accelerated kinase activation due to activation loop mutations.

Conclusions:

  • Acquired resistance is a significant challenge in kinase inhibitor therapy.
  • Novel strategies are emerging to circumvent resistance and restore drug sensitivity.
  • Further research into resistance mechanisms will guide the development of more effective cancer treatments.

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