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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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TRK Inhibitors: Tissue-Agnostic Anti-Cancer Drugs

Sun-Young Han1

  • 1Research Institute of Pharmaceutical Sciences and College of Pharmacy, Gyeongsang National University, Jinju-si 52828, Korea.

Pharmaceuticals (Basel, Switzerland)
|July 2, 2021
PubMed

Insights

Larotrectinib and entrectinib, tropomyosin receptor kinase (Trk) inhibitors, target Trk fusions across cancer types. Tissue-agnostic development accelerated their approval and companion diagnostics.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Tropomyosin receptor kinase (Trk) fusions are key drivers in various cancers.
  • Larotrectinib and entrectinib are approved Trk inhibitors offering a new treatment paradigm.

Purpose of the Study:

  • To review the development of larotrectinib and entrectinib.
  • To discuss other Trk inhibitors in clinical trials.
  • To highlight the impact of tissue-agnostic development and companion diagnostics.

Main Methods:

  • Review of clinical trial data for larotrectinib and entrectinib.
  • Analysis of tissue-agnostic development strategies.
  • Discussion of next-generation sequencing-based companion diagnostics.

Main Results:

  • Tissue-agnostic development expedited Trk inhibitor approvals.
  • Next-generation sequencing companion diagnostics enable Trk fusion detection.
  • On-target effects include central nervous system adverse events.

Conclusions:

  • Tissue-agnostic development is an effective strategy for targeted cancer therapies.
  • Companion diagnostics are crucial for identifying patients eligible for Trk inhibitors.
  • Further research into Trk inhibitors and their side effects is warranted.
Keywords:
NTRKTrkTrk fusionentrectiniblarotrectinibtissue-agnostic

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