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Updated: Mar 6, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.4K

Mutation type, tyrosine kinase function in normal cell and tyrosine kinase inhibitor activity in cancers

H Vanacker1,2, P A Cassier1,2, A Dufresne1,2

  • 1Centre Léon Bérard, rue Laennec, Lyon, 69008, France.

Scientific Reports
|March 4, 2026
PubMed

Insights

The function of receptor tyrosine kinases (RTKs) in normal cells can predict the effectiveness of tyrosine kinase inhibitors (TKIs) in corresponding cancers. This finding aids in selecting cancers for developing new targeted cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Clinical activity of tyrosine kinase inhibitors (TKIs) varies in cancers with similar receptor tyrosine kinase (RTK) mutations.
  • Predicting TKI efficacy remains a challenge in precision oncology.

Purpose of the Study:

  • To test if RTK function in normal cells can predict TKI activity in corresponding cancers.
  • To identify biomarkers for TKI efficacy in solid tumors.

Main Methods:

  • Analyzed 16 RTKs across 17 solid tumors using public databases.
  • Investigated RTK alterations (missense mutations, amplifications, translocations) as biomarkers for TKI efficacy in pivotal trials.

Main Results:

  • TKIs showed minimal activity in cancers with RTK amplification.
  • TKI efficacy correlated with RTK mutation type and the RTK's role in normal cells.
  • Missense mutations predicted TKI efficacy when RTKs are crucial in normal cells; translocations were tissue-agnostic.

Conclusions:

  • RTK function in normal cells is a predictive biomarker for TKI efficacy.
  • Mutation type and cellular context influence TKI response.
  • Guidance for selecting cancers for novel targeted therapy development.

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