# ROS1

Source: https://onco.cc/targets/ros1/  
OnCo record `ros1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.

## Summary

ROS1 rearrangements (CD74-ROS1 most common) occur in ~1-2% of NSCLC, typically in younger never-smokers. Crizotinib (2016) and entrectinib (2019) were first; repotrectinib (2023) covers the G2032R solvent-front mutation; zidesamtinib (July 2026) adds TRK sparing to reduce neurologic toxicity. Also seen in cholangiocarcinoma and glioblastoma (rare).

## Fields

- Kind: Target
- Last checked: 2026-09-06
- Tags: driver; kinase
- Symbol: ROS1
- Class: kinase
- Biology: Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.
- Where found: NSCLC (~1-2%); Cholangiocarcinoma, glioblastoma, Spitz tumours (rare); Non-small-cell lung cancer: rearrangement, commonly cd74-ros1 1-3%

## Notes

- Lung cancer: rearranged in 1 to 3% of adenocarcinomas, commonly with CD74, and concentrated in younger never smokers with adenocarcinoma histology (Bergethon 2012; cBioPortal). ROS1 missense variants read high on exome panels, including 7.6% of squamous tumours, and are passengers. Testing is recommended for every patient with lung adenocarcinoma, with immunohistochemistry acceptable as a screen (Lindeman 2018).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/ROS1
- Wikipedia: https://en.wikipedia.org/wiki/ROS1

## Connected records

- biomarkers: [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)
- cancers: [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/)
- drugs: [Crizotinib](https://onco.cc/drugs/crizotinib/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Iruplinalkib](https://onco.cc/drugs/iruplinalkib/), [Oncomine Dx Target Test](https://onco.cc/drugs/oncomine-dx-target-test/), [Repotrectinib](https://onco.cc/drugs/repotrectinib/), [Taletrectinib](https://onco.cc/drugs/taletrectinib/), [Zidesamtinib](https://onco.cc/drugs/zidesamtinib/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/)
- key papers: [ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/), [Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/), [NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [ROS1 rearrangements define a unique molecular class of lung cancers](https://onco.cc/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- pairings: [Sequence: targeted therapy before immunotherapy in driver-positive NSCLC](https://onco.cc/pairings/targeted-before-io-nsclc/)
- trials: [PROFILE 1001 ROS1 expansion cohort](https://onco.cc/trials/profile-1001-ros1/)
- people: [Alexander Drilon](https://onco.cc/people/alexander-drilon/), [Dong-Wan Kim](https://onco.cc/people/kim-dong-wan/), [Koichi Goto](https://onco.cc/people/goto-koichi/)
- collections: [LUNGevity Foundation (and GO2 for Lung Cancer)](https://onco.cc/collections/lungevity/)
- institutions: [nationales Netzwerk Genomische Medizin Lungenkrebs](https://onco.cc/institutions/nngm/), [University of Colorado Cancer Center](https://onco.cc/institutions/colorado-cancer-center/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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JSON: https://onco.cc/api/v1/entities/ros1.json