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Updated: Sep 2, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

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Research Progress on Small Molecules Inhibitors Targeting TRK Kinases

Ju Liu1,2,3, Yadong Zhang1, Yan Zhu1

  • 1College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, P. R. China.

Current Medicinal Chemistry
|August 5, 2022
PubMed
Abstract

Insights

Trk gene fusions drive cancers, and while first-generation inhibitors exist, research now focuses on second-generation TRK inhibitors to overcome drug resistance. This review details progress in both drug classes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Trk gene fusions are key drivers in various cancers, including secretory breast cancer and infantile congenital sarcoma.
  • The advent of first-generation TRK inhibitors (Larotrectinib, Entrectinib) marked a milestone, but drug resistance remains a challenge.

Purpose of the Study:

  • To review the research progress of first-generation TRK inhibitors.
  • To highlight the development of second-generation TRK inhibitors designed to overcome drug resistance.

Main Methods:

  • Literature search of relevant and cutting-edge documents.
  • Filtering, selection, analysis, and classification of appropriate articles.
  • Synthesis of information to address specific research topics.

Main Results:

  • Description of Trk protein fusions and their oncogenic role.
  • Explanation of Trk kinase composition and signaling pathways.
  • Classification of TRK inhibitors based on their ability to overcome drug resistance.

Conclusions:

  • Provides a theoretical reference for developing novel TRK inhibitors.
  • Summarizes representative and novel TRK inhibitors that address drug resistance.
Keywords:
Trk gene fusionsTrk inhibitorsTrk kinasesdrug resistanceovercoming drug resistancetumors

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