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Updated: Mar 18, 2026

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Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer.

Curtis R Chong1, Magda Bahcall1, Marzia Capelletti1

  • 1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 3, 2016
PubMed
Summary
This summary is machine-generated.

Existing drugs may overcome resistance in rare cancers. Cabozantinib shows promise for treating ROS1-rearranged non-small cell lung cancer (NSCLC) after crizotinib progression.

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Area of Science:

  • Oncology
  • Drug Discovery
  • Molecular Biology

Background:

  • Drug resistance to targeted therapies in rare oncogenic alterations like NTRK1 and ROS1 rearrangements presents a significant challenge.
  • The discovery of novel drugs for these alterations is often hampered by high costs and lengthy development timelines.

Purpose of the Study:

  • To identify inhibitors of NTRK1 and ROS1, key oncogenes in some non-small cell lung cancer (NSCLC) cases.
  • To explore the potential repurposing of existing targeted drugs to overcome resistance.

Main Methods:

  • A library of existing targeted drugs was screened against Ba/F3 cells engineered to express NTRK1 and ROS1 fusions.
  • Inhibitory concentrations (IC50) of identified drugs were determined for various oncogenic mutants.
  • In vitro assays assessed drug effects on oncogene autophosphorylation and downstream signaling pathways.

Main Results:

  • Cabozantinib emerged as a potent inhibitor of CD74-ROS1 fusions, including crizotinib-resistant mutants (G2032R and L2026M).
  • Cabozantinib demonstrated superior potency compared to other targeted agents like brigatinib, entrectinib, and PF-06463922 against ROS1 fusions.
  • BMS-536924 potently inhibited CD74-NTRK1 fusions.
  • A patient with metastatic ROS1-rearranged NSCLC who progressed on crizotinib achieved a partial response with cabozantinib treatment.

Conclusions:

  • Existing drugs can be repurposed to overcome acquired resistance to targeted therapies.
  • Cabozantinib is identified as a promising therapeutic option for patients with ROS1-rearranged NSCLC who have progressed on crizotinib.