ArticleEMBO molecular medicine2023
Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- In vitro and in silico modelling of ROS1-positive non-small cell lung cancer reveals fusion-dependent tyrosine kinase inhibitor responses.Molecular oncology · 2026Article
- [Clinicopathological Characteristics of ROS1-positive Non-small Cell Lung Cancer Based on Next-generation Sequencing].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Response to crizotinib treatment for ROS1 p.H1999N mutation and secondary EGFR p.V774M mutation after drug resistance: a Case Report.Frontiers in pharmacology · 2026Article
- Multidisciplinary management and molecular characterization of inferior vena cava leiomyosarcoma: a case report.World journal of surgical oncology · 2025Article
- Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- CRISPR/Cas9-edited ROS1 + non-small cell lung cancer cell lines highlight differential drug sensitivity in 2D vs 3D cultures while reflecting established resistance profiles.Journal of translational medicine · 2024Article
- Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors.EMBO molecular medicine · 2023Article
- Exploring the Profiles of ROS1 Tyrosine Kinase: A Structural Analysis of G2032R and D2033N Mutations.International journal of applied & basic medical researchArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
ROS1 is the largest receptor tyrosine kinase in the human genome. Rearrangements of the ROS1 gene result in oncogenic ROS1 kinase fusion proteins that are currently the only validated biomarkers for targeted therapy with ROS1 TKIs in patients. While numerous somatic missense mutations in ROS1 exist in the cancer genome, their impact on catalytic activity and pathogenic potential is unknown. We interrogated the AACR Genie database and identified 34 missense mutations in the ROS1 tyrosine kinase domain for further analysis. Our experiments revealed that these mutations have varying effects on ROS1 kinase function, ranging from complete loss to significantly increased catalytic activity. Notably, Asn and Gly substitutions at Asp2113 in the ROS1 kinase domain were found to be TKI-sensitive oncogenic variants in cell-based model systems. In vivo experiments showed that ROS1 D2113N induced tumor formation that was sensitive to crizotinib and lorlatinib, FDA-approved ROS1-TKIs. Collectively, these findings highlight the tumorigenic potential of specific point mutations within the ROS1 kinase domain and their potential as therapeutic targets with FDA-approved ROS1-TKIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.