{"entity":{"id":"ros1","kind":"target","name":"ROS1","aka":[],"tldr":"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).","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/ROS1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/ROS1"}],"tags":["driver","kinase"],"related":["ros1-fusion"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["repotrectinib","zidesamtinib","taletrectinib","oncomine-dx-target-test"],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":["gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bergethon-ros1-rearrangements-lung-jco-2012"],"journals":[],"dependsOn":[],"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)."],"symbol":"ROS1","role":[],"sources":[],"specificity":"tumour-specific","distribution":"many-types","tumourAgnostic":true,"specificityNote":"Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (ROS1 fusion (ROS1-positive)) absent from normal cells. HPA ROS1: RNA group enriched (epididymis 55 nTPM, lung 30 nTPM); no normal tissue stained high; highest cancer staining liver cancer (1 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Lung cancer (all types)); Open Targets associates it with 2 specific cancer types at or above 0.5 (non-small cell lung carcinoma, lung adenocarcinoma). Tissue-agnostic: Entrectinib US 2019: \"ROS1-positive metastatic NSCLC; NTRK fusion solid tumours (≥12 years, extended to ≥1 month 2023)\". (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"ROS1 fusion (ROS1-positive) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908","note":"ROS1-positive"},{"label":"Human Protein Atlas ROS1 tissue","url":"https://www.proteinatlas.org/ENSG00000047936-ROS1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000047936 associations","url":"https://platform.opentargets.org/target/ENSG00000047936/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:10261","ensembl":"ENSG00000047936","uniprot":"P08922","entrez":"6098","firstDescribed":1986,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Matsushime et al, Mol. Cell. Biol, 1986, \"Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3023956/","biology":"Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.","whereFound":["NSCLC (~1-2%)","Cholangiocarcinoma, glioblastoma, Spitz tumours (rare)","Non-small-cell lung cancer: rearrangement, commonly cd74-ros1 1-3%"],"targetClass":"kinase","prevalence":[{"cancerId":"nsclc","pct":1.7,"measure":"FISH, ROS1 rearrangement (18 of 1,073 NSCLC)","source":"https://doi.org/10.1200/JCO.2011.35.6345","note":"Bergethon 2012; enriched in younger never-smokers with adenocarcinoma"},{"cancerId":"nsclc","pct":"1-3","measure":"Rearrangement, commonly CD74-ROS1","source":"https://www.cbioportal.org/study/summary?id=lung_msk_2017","note":"cBioPortal structural variants: 25 of 915, 2.7%, in lung_msk_2017 (CD74 in 13 events, EZR in 4, SDC4 in 3, SLC34A2 in 2); 44 of 2,621, 1.7%, in nsclc_ctdx_msk_2022; 40 of 2,422, 1.7%, in luad_mskcc_2023_met_organotropism; 5 of 232, 2.2%, in lung_nci_2022. In the founding series, 18 of 1,073 screened lung cancers, 1.7%, against 31 ALK-rearranged, 2.9% (Bergethon 2012)."}]},"route":"/targets/ros1/","neighbours":{"biomarker":[{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"}],"cancer":[{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ntrk-fusion-nsclc","kind":"cancer","name":"NTRK fusion-positive non-small-cell lung cancer","route":"/cancers/ntrk-fusion-nsclc/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"}],"drug":[{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"iruplinalkib","kind":"drug","name":"Iruplinalkib","route":"/drugs/iruplinalkib/"},{"id":"oncomine-dx-target-test","kind":"drug","name":"Oncomine Dx Target Test","route":"/drugs/oncomine-dx-target-test/"},{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"},{"id":"taletrectinib","kind":"drug","name":"Taletrectinib","route":"/drugs/taletrectinib/"},{"id":"zidesamtinib","kind":"drug","name":"Zidesamtinib","route":"/drugs/zidesamtinib/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"}],"paper":[{"id":"paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","kind":"paper","name":"ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer","route":"/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/"},{"id":"paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","kind":"paper","name":"Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer","route":"/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/"},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","route":"/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/"},{"id":"paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","kind":"paper","name":"NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer","route":"/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/"},{"id":"paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","kind":"paper","name":"Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies","route":"/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/"},{"id":"paper-bergethon-ros1-rearrangements-lung-jco-2012","kind":"paper","name":"ROS1 rearrangements define a unique molecular class of lung cancers","route":"/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/"},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","route":"/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/"}],"pairing":[{"id":"targeted-before-io-nsclc","kind":"pairing","name":"Sequence: targeted therapy before immunotherapy in driver-positive NSCLC","route":"/pairings/targeted-before-io-nsclc/"}],"trial":[{"id":"profile-1001-ros1","kind":"trial","name":"PROFILE 1001 ROS1 expansion cohort","route":"/trials/profile-1001-ros1/"}],"person":[{"id":"alexander-drilon","kind":"person","name":"Alexander Drilon","route":"/people/alexander-drilon/"},{"id":"kim-dong-wan","kind":"person","name":"Dong-Wan Kim","route":"/people/kim-dong-wan/"},{"id":"goto-koichi","kind":"person","name":"Koichi Goto","route":"/people/goto-koichi/"}],"collection":[{"id":"lungevity","kind":"collection","name":"LUNGevity Foundation (and GO2 for Lung Cancer)","route":"/collections/lungevity/"}],"institution":[{"id":"nngm","kind":"institution","name":"nationales Netzwerk Genomische Medizin Lungenkrebs","route":"/institutions/nngm/"},{"id":"colorado-cancer-center","kind":"institution","name":"University of Colorado Cancer Center","route":"/institutions/colorado-cancer-center/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}