TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults

Related Experiment Video

Updated: Sep 29, 2025

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

15.0K

Guilherme Harada1, Alexander Drilon2

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York 10065, USA; Oncology Center, Sirio-Libanes Hospital, Rua Dona Adma Jafet, 91, Sao Paulo CEP 01308-050, Brazil.

Cancer Genetics
|March 25, 2022
PubMed

Insights

TRK inhibitors like larotrectinib offer effective treatment for NTRK fusion-driven adult cancers, with newer agents addressing resistance. Understanding side effects and resistance is key for optimal outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • NTRK fusions are key drivers of oncogenesis in various adult cancers.
  • First-generation TRK inhibitors (larotrectinib, entrectinib) revolutionized tumor-agnostic therapy.
  • These drugs show high response rates, durable control, and intracranial activity.

Purpose of the Study:

  • To review the clinical efficacy of TRK inhibitors in adult cancers.
  • To discuss the safety profiles and on-target side effects of TRK inhibition.
  • To explore resistance mechanisms and the development of next-generation TRK inhibitors.

Main Methods:

  • Review of clinical trial data and scientific literature.
  • Analysis of efficacy, safety, and resistance patterns of TRK inhibitors.
  • Focus on data pertaining to adult cancer patients.

Main Results:

  • First-generation TRK inhibitors demonstrate significant clinical benefits.
  • Common on-target side effects include dizziness, weight gain, and withdrawal pain.
  • Next-generation inhibitors (selitrectinib, repotrectinib, taletrectinib) show efficacy against specific resistance mutations.

Conclusions:

  • TRK inhibitors are crucial in treating NTRK fusion-positive adult cancers.
  • Managing on-target toxicities is essential for patient care.
  • Ongoing research into resistance mechanisms fuels the development of more effective therapies.
Keywords:
NTRK gene fusionsTRKTRK fusion cancerTRK inhibitors

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