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Updated: Jan 3, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Targeted therapies for ROS1-rearranged non-small cell lung cancer
T Patil1, E Simons2, R Mushtaq1
1Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Abstract:
ROS1 gene fusions account for approximately 1-2% of all cases of non-small cell lung cancer (NSCLC). Similarly to anaplastic lymphoma kinase (ALK)-positive NSCLC, patients with ROS1+ NSCLC tend to have minimal smoking and be of the female sex. In most cases, adenocarcinoma is the dominant histology. The ROS1 gene has homology to ALK and this structural similarity formed the basis for utilizing ALK inhibitors for ROS1+ NSCLC. On the basis of impressive progression-free survival of 19.2 months from the PROFILE 1001 trial, crizotinib obtained Food and Drug Administration (FDA) approval as first-line therapy for treatment of ROS1+ NSCLC. Since then, there has been a growing appreciation of the incidence of brain metastases in ROS1+ NSCLC and rates of central nervous system progression on crizotinib. Additionally, appreciation of novel resistance mechanisms to crizotinib has led to the development of newer tyrosine kinase inhibitors (TKIs). In this review, we highlight known and emerging TKIs for the management of ROS1+ NSCLC.
Insights
ROS1 gene fusions are key in non-small cell lung cancer (NSCLC). This review covers tyrosine kinase inhibitors (TKIs) for ROS1-positive NSCLC, including newer agents addressing resistance and brain metastases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- ROS1 gene fusions occur in 1-2% of non-small cell lung cancer (NSCLC) cases.
- ROS1-positive NSCLC shares characteristics with ALK-positive NSCLC, including lower smoking history and female predominance.
- Adenocarcinoma is the most common histology in ROS1-positive NSCLC.
Purpose of the Study:
- To review current and emerging tyrosine kinase inhibitors (TKIs) for ROS1-positive NSCLC.
- To discuss the management of brain metastases and central nervous system progression in ROS1-positive NSCLC.
- To highlight novel resistance mechanisms to crizotinib and the development of next-generation TKIs.
Main Methods:
- Literature review of clinical trials and research studies on ROS1-positive NSCLC.
- Analysis of progression-free survival data and treatment outcomes.
- Examination of molecular mechanisms of resistance to TKIs.
Main Results:
- Crizotinib demonstrated significant progression-free survival (19.2 months) in the PROFILE 1001 trial, leading to FDA approval.
- Brain metastases and central nervous system progression are significant concerns in ROS1-positive NSCLC.
- Emerging TKIs show promise in overcoming resistance to crizotinib and managing advanced disease.
Conclusions:
- Tyrosine kinase inhibitors are crucial for managing ROS1-positive NSCLC.
- Ongoing research is focused on developing more effective TKIs to address resistance and CNS involvement.
- Personalized treatment strategies incorporating newer TKIs are essential for improving outcomes in ROS1-positive NSCLC.
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