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Updated: Jan 22, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
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Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase

Tessa A Morris1, Christine Khoo2, Benjamin J Solomon3,4

  • 1Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.

Drugs
|July 18, 2019
PubMed

Insights

ROS1 gene rearrangements drive 1-2% of non-small cell lung cancers. While crizotinib is a first-line therapy, resistance develops, necessitating research into newer targeted treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ROS1 gene rearrangements are oncogenic drivers in 1-2% of non-small cell lung cancers (NSCLC).
  • These rearrangements typically occur in younger, never/light smokers with adenocarcinoma histology.
  • ROS1 fusions confer sensitivity to ROS1-targeted therapies.

Purpose of the Study:

  • To review ROS1 rearrangements in NSCLC.
  • To update on targeting ROS1-rearranged NSCLC with crizotinib and newer tyrosine kinase inhibitors.

Main Methods:

  • Literature review of ROS1 rearrangements and targeted therapies in NSCLC.
  • Discussion of crizotinib efficacy and resistance mechanisms.
  • Evaluation of emerging next-generation tyrosine kinase inhibitors.

Main Results:

  • Crizotinib is the first-line therapy for advanced ROS1-rearranged NSCLC, showing initial efficacy.
  • Most patients develop resistance to crizotinib, leading to disease progression (intracranial and extracranial).
  • Newer TKIs with enhanced potency and intracranial activity are under clinical investigation.

Conclusions:

  • Targeting ROS1 rearrangements is crucial in a subset of NSCLC patients.
  • Overcoming resistance to crizotinib and other TKIs is an active area of research.
  • Next-generation inhibitors offer promise for improved outcomes in ROS1-rearranged NSCLC.

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