Related Experiment Video

Updated: Jul 7, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

9.6K

Oncogenic fusions: Targeting NTRK

Garo Hagopian1, Misako Nagasaka2

  • 1Department of Medicine, University of California Irvine Medical Center, Orange, CA, USA.

Critical Reviews in Oncology/Hematology
|December 20, 2023
PubMed

Insights

Neurotrophic tyrosine receptor kinase (NTRK) fusions drive Non-Small Cell Lung Cancer (NSCLC). Established therapies face challenges, but novel treatments targeting NTRK-mutated NSCLC are emerging.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Non-Small Cell Lung Cancer (NSCLC) is a leading cause of cancer mortality in the U.S.
  • Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are key oncogenic drivers in various cancers, including NSCLC.
  • Current FDA-approved therapies for NTRK-mutated cancers include larotrectinib and entrectinib.

Purpose of the Study:

  • To review established and novel therapeutic strategies for NSCLC with NTRK fusions.
  • To discuss the clinical challenges associated with current NTRK-targeted therapies.
  • To highlight the ongoing development of new tyrosine kinase inhibitors for NTRK-mutated NSCLC.

Main Methods:

  • Literature review of established and emerging therapies for NTRK-mutated NSCLC.
  • Analysis of clinical hurdles such as resistance mutations and central nervous system (CNS) penetration.
  • Exploration of ongoing clinical trials for novel tyrosine kinase inhibitors.

Main Results:

  • Larotrectinib and entrectinib show efficacy but face limitations including resistance and CNS penetration.
  • Numerous novel tyrosine kinase inhibitors targeting NTRK fusions are in early-phase clinical development.
  • The treatment landscape for NTRK-mutated NSCLC is evolving with promising new therapeutic options.

Conclusions:

  • Targeting NTRK fusions represents a significant advancement in NSCLC treatment.
  • Overcoming resistance and improving CNS penetration are critical for enhancing therapeutic outcomes.
  • Continued research and clinical trials are essential to expand treatment options for patients with NTRK-mutated NSCLC.
Keywords:
EntrectinibLarotrectinibNeurotrophic tyrosine receptor kinaseRepotrectinibTRK related adverse events

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