Affinage

ROS1

Proto-oncogene tyrosine-protein kinase ROS · UniProt P08922

Length
2347 aa
Mass
263.9 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ROS1 is a transmembrane receptor tyrosine kinase that is transiently expressed during organ morphogenesis and is converted into a potent oncogenic driver by chromosomal rearrangement (PMID:1718742, PMID:22327623). The gene was first identified as a tyrosine kinase-related oncogene activated by loss of its extracellular domain, with cell-type-specific expression in glioblastoma lines (PMID:3785223, PMID:2827175). In normal development, c-ros is transiently expressed in kidney ureter epithelium, intestine, and lung, where it acts in mesenchymal–epithelial inductive interactions (PMID:1718742). In cancer, gene fusions that retain the ROS1 kinase domain define a molecular subgroup of NSCLC and render the kinase constitutively active, driving proliferation through the Ras/Raf/MEK/ERK module, survival through PI3K, and migration through Vav3 (PMID:22327623, PMID:23719267, PMID:28465216). ROS1 kinase activity is also engaged by reductive stress: GPX1 deficiency causes glutathione accumulation and s-glutathiolation of the ROS1-associated phosphatase SHP-2, relieving its inhibition and permitting ROS1 autophosphorylation at Y2274 to drive vascular smooth muscle cell proliferation (PMID:25401476). ROS1 inhibition is synthetically lethal in E-cadherin (CDH1)-deficient breast cancer cells, where it is required for normal cytokinesis and proper p120 catenin localization (PMID:29610289). Clinically, crizotinib produces marked responses in ROS1-rearranged NSCLC, establishing ROS1 as a validated therapeutic target (PMID:25264305), but resistance arises predominantly through kinase domain mutations—most commonly the solvent-front G2032R, with L2086F and F2004C conferring distinct, inhibitor-class-dependent resistance profiles addressable by selective, type II, or macrocyclic inhibitors (PMID:30093503, PMID:31399568, PMID:33685866, PMID:34907086).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1986 Medium

    Establishing that ROS1 is a tyrosine kinase whose oncogenic form arises from loss of its extracellular domain answered whether MCF3 was a kinase oncogene and how it became activated.

    Evidence DNA-mediated gene transfer, tumorigenicity assay, and cDNA structural analysis

    PMID:3785223

    Open questions at the time
    • No ligand or physiological substrate identified
    • Activation mechanism inferred from structure, not biochemically reconstituted
  2. 1987 Medium

    Mapping ROS1 expression and locus alterations in cancer cell lines established cell-type-specific expression and susceptibility to activating mutation, hinting at a role in malignancy.

    Evidence Northern/Southern blot survey of 45 cell lines, chromosomal mapping to 6q

    PMID:2827175 PMID:3329713

    Open questions at the time
    • Functional consequence of the glioblastoma-line mutation not validated
    • No mechanistic link from 6q rearrangement to ROS1 activation
  3. 1991 Medium

    Demonstrating transient, tissue-restricted c-ros expression during organogenesis defined a normal developmental function as a receptor tyrosine kinase in inductive epithelial–mesenchymal interactions.

    Evidence RNase protection assay and in situ hybridization in mouse development

    PMID:1718742

    Open questions at the time
    • Ligand remains unknown
    • Downstream developmental signaling not defined
  4. 2012 High

    Identifying recurrent ROS1 fusions in lung adenocarcinoma defined a distinct oncogenic NSCLC subgroup and shifted ROS1 from orphan oncogene to actionable driver.

    Evidence RT-PCR and FISH screening across 1,529 lung cancers

    PMID:22327623

    Open questions at the time
    • Mechanism of constitutive activation for non-dimerizing partners not resolved
    • Partner-specific signaling differences not addressed
  5. 2013 Medium

    Linking ROS1 fusions to defined downstream cascades explained how the constitutively active kinase drives proliferation, survival, and migration.

    Evidence Synthesis of preclinical cell-based and in vivo signaling studies

    PMID:23719267

    Open questions at the time
    • Relative contribution of each pathway to transformation not quantified
    • Direct substrates not enumerated
  6. 2014 High

    A phase I expansion cohort showing 72% response to crizotinib clinically validated ROS1 kinase activity as the oncogenic driver and therapeutic target in ROS1-rearranged NSCLC.

    Evidence Phase I clinical trial (n=50) with NGS/RT-PCR fusion typing

    PMID:25264305

    Open questions at the time
    • Did not define resistance mechanisms
    • No correlation found between partner type and response, leaving partner biology open
  7. 2014 High

    Defining the GPX1–glutathione–SHP-2–ROS1 axis revealed a redox-regulated, non-oncogenic ROS1 activation mechanism driving pathological vascular remodeling.

    Evidence Gpx1 knockout mice, glutathiolation biochemistry, crizotinib inhibition, human cohort GWAS meta-analysis

    PMID:25401476

    Open questions at the time
    • How ROS1 senses or couples to reductive stress upstream of SHP-2 not fully resolved
    • Endogenous ligand still unidentified
  8. 2015 High

    Structural comparison of ROS1 and ALK kinase domains explained inhibitor selectivity and showed that ROS1-selective inhibitors retain activity against the G2032R solvent-front mutant that escapes crizotinib.

    Evidence Molecular dynamics simulation and Ba/F3/patient-derived cell resistance profiling across seven compounds

    PMID:26372962

    Open questions at the time
    • Predictions for some mutants based on modeling rather than crystal structures
    • Clinical activity of selective agents not yet established at this stage
  9. 2018 High

    Discovering synthetic lethality between ROS1 inhibition and CDH1 loss revealed a non-canonical ROS1 requirement in cytokinesis and a therapeutic vulnerability in E-cadherin-deficient breast cancer.

    Evidence CRISPR CDH1 engineering, genetic screens, pharmacological inhibition, mitotic imaging, and in vivo tumor models

    PMID:29610289

    Open questions at the time
    • Direct ROS1 substrate controlling cytokinesis not identified
    • Mechanistic basis of CDH1-dependence not fully defined
  10. 2018 High

    Repotrectinib provided in vitro, in vivo, and clinical proof that macrocyclic TKIs overcome solvent-front (G2032R, D2033N) resistance, mapping resistance to the kinase active site.

    Evidence Kinase assays, mouse models, and phase I/II first-in-human trial

    PMID:30093503

    Open questions at the time
    • Durability and resistance to repotrectinib not yet defined
    • Coverage of non-solvent-front mutations not fully tested
  11. 2021 High

    Systematic clinical sequencing and functional screens established kinase domain mutations as the dominant resistance mechanism and resolved inhibitor-class-specific profiles for G2032R, L2086F, and F2004C.

    Evidence Clinical biopsy NGS, Ba/F3 functional assays, structural modeling, forward mutagenesis screens, and DS-6051b/cabozantinib profiling

    PMID:31399568 PMID:33685866 PMID:34907086

    Open questions at the time
    • No single inhibitor covers all resistance mutations
    • Compound/sequential resistance evolution not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous human ROS1 ligand and the mechanism of constitutive activation for non-dimerizing fusion partners remain undefined.
  • Human ROS1 ligand unknown
  • Activation mechanism of CD74-ROS1 and other non-dimerizing fusions unresolved
  • Partner-dependent localization-to-substrate link not experimentally demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-1266738 Developmental Biology 1 R-HSA-1640170 Cell Cycle 1
Partners
CD74EZRGPX1SHP-2

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The human ROS1 oncogene (previously called MCF3) encodes a protein with homology to tyrosine-specific protein kinases, possesses a putative transmembrane domain N-terminal to the kinase domain, and likely arose from a normal human ROS1 gene by loss of a putative extracellular domain during gene transfer. The activated MCF3 form lacks gross rearrangements beyond loss of the extracellular domain. DNA-mediated gene transfer, tumorigenicity assay, structural analysis of cDNA Molecular and cellular biology Medium 3785223
1987 ROS1 is expressed at high levels specifically in glioblastoma-derived cell lines (but not in other cell lines) without gene amplification, and a potentially activating mutation at the ROS1 locus was detected in one glioblastoma line, indicating cell-type-specific expression and susceptibility to activating mutation. Northern blot survey of 45 cell lines, Southern blot copy-number analysis Proceedings of the National Academy of Sciences of the United States of America Medium 2827175
1987 The human ROS1 gene (formerly MCF3) maps to the distal half of chromosome 6q, a region frequently rearranged in malignant cells, suggesting involvement in diverse tumor types. Chromosomal mapping (somatic cell hybrid panel) Oncogene research Low 3329713
1991 During mouse development, c-ros1 is transiently expressed in the kidney, intestine, and lung coinciding with major morphogenetic events; in the kidney, expression is confined to ureter epithelial cells involved in inductive interactions with metanephric mesenchyme, implicating ROS1 as a receptor tyrosine kinase in mesenchymal–epithelial inductive interactions. RNase protection assay, in situ hybridization The EMBO journal Medium 1718742
2012 ROS1 gene fusions (with multiple partner genes) were identified in lung adenocarcinoma by integrated molecular screening; the resulting fusion proteins retain the ROS1 kinase domain and act as oncogenic drivers, defining a molecular subgroup of NSCLC. RT-PCR, fluorescence in situ hybridization (FISH), integrated histopathology-based screening in 1,529 lung cancers Nature medicine High 22327623
2013 ROS1 chromosomal rearrangements create fusion proteins in which the ROS1 kinase domain becomes constitutively active and drives cellular proliferation; downstream signaling from ROS1 fusion proteins activates the Ras/Raf/MEK/ERK1/2 proliferation module, the PI3K cell survival pathway, and the Vav3 cell migration pathway. Review/synthesis of preclinical cell-based assays and in vivo models reported across multiple studies Clinical cancer research Medium 23719267
2014 ROS1 inhibition with crizotinib showed marked antitumor activity in ROS1-rearranged NSCLC patients (72% objective response rate), establishing ROS1 kinase activity as an oncogenic driver and therapeutic target in this cancer subgroup. Seven distinct ROS1 fusion partners were identified; no correlation was observed between fusion partner type and clinical response to crizotinib. Phase I expansion cohort clinical trial (n=50), next-generation sequencing and RT-PCR for fusion partner identification, pharmacokinetics assessment The New England journal of medicine High 25264305
2014 ROS1 kinase is activated by reductive stress downstream of GPX1 deficiency: loss of GPX1 leads to glutathione accumulation (reductive stress), which causes s-glutathiolation of the ROS1-associated phosphatase SHP-2, inhibiting SHP-2 and permitting ROS1 phosphorylation at activation site Y2274, thereby promoting vascular smooth muscle cell proliferation and pathological vascular remodeling. ROS1 inhibition with crizotinib abolished this proliferative effect without impairing endothelialization. Constitutive Gpx1 knockout mouse model, gene variant pair analysis in patient cohorts, genome-wide association meta-analysis, glutathiolation biochemistry, crizotinib pharmacological inhibition, in vivo vascular remodeling assay The Journal of clinical investigation High 25401476
2015 Structural and molecular dynamics studies of the ROS1 kinase domain revealed distinct structural features distinguishing ROS1 from ALK that underlie differences in inhibitor selectivity. Cabozantinib and foretinib show striking selectivity for ROS1 over ALK. Cell-based resistance profiling demonstrated that ROS1-selective inhibitors retain efficacy against the CD74-ROS1(G2032R) solvent-front mutation whereas dual ROS1/ALK inhibitors (including crizotinib) are ineffective against this mutation. Molecular dynamics simulation, cell-based resistance profiling (Ba/F3 and patient-derived cell models), inhibitor selectivity assays across seven compounds Proceedings of the National Academy of Sciences of the United States of America High 26372962
2016 ROS1 fusion protein subcellular localization differs depending on the fusion partner: partners that retain transmembrane domains or dimerization domains influence whether ROS1 fusions localize to different subcellular compartments, suggesting that distinct fusions activate different substrates in vivo. Unlike ALK fusion proteins (activated by amino-terminal dimerization), several ROS1 fusion partners including CD74 apparently lack dimerization ability, leaving the mechanism of constitutive kinase activation for those fusions unknown. Literature synthesis, structural analysis of fusion protein domains Future oncology Low 27256160
2017 ROS1 protein-tyrosine kinase fusion proteins signal downstream through the Ras/Raf/MEK/ERK1/2 cell proliferation module, the PI3K cell survival pathway, and the Vav3 cell migration pathway. Crizotinib forms a complex within the front cleft between the small and large lobes of an active ROS1 protein-kinase domain and is classified as a type I inhibitor. Review of cell-based signaling studies; structural classification of inhibitor binding mode Pharmacological research Medium 28465216
2018 Repotrectinib (TPX-0005), a macrocyclic TKI, is highly potent against ROS1 (including the solvent-front mutations G2032R and D2033N) and overcomes resistance to earlier-generation ROS1 inhibitors both in vitro and in vivo; confirmed responses were achieved in patients with ROS1 fusion-positive cancers that had relapsed on earlier-generation TKIs due to solvent-front substitution-mediated resistance. In vitro kinase assays, in vivo mouse models, phase I/II first-in-human clinical trial Cancer discovery High 30093503
2018 ROS1 inhibition is synthetically lethal with E-cadherin (CDH1) deficiency in breast cancer cells. ROS1 inhibitors (foretinib, crizotinib) induced mitotic abnormalities, multinucleation, defective cytokinesis, and aberrant p120 catenin phosphorylation and localization specifically in E-cadherin-defective cells. In vivo, ROS1 inhibitors produced profound antitumor effects in multiple models of E-cadherin-defective breast cancer. CRISPR/Cas9-engineered CDH1 mutations, large-scale genetic perturbation screens in molecularly diverse breast tumor cell lines, pharmacological inhibition (foretinib, crizotinib), immunofluorescence for mitotic phenotypes, p120 catenin localization assays, in vivo mouse tumor models Cancer discovery High 29610289
2019 DS-6051b, a selective ROS1/NTRK inhibitor, inhibits both wild-type ROS1 fusions and the crizotinib-resistant G2032R mutant ROS1 in vitro and in vivo, demonstrating that the G2032R solvent-front mutation is highly resistant to crizotinib, lorlatinib, and entrectinib but sensitive to DS-6051b. Cell-based growth inhibition assays (in vitro), xenograft mouse models (in vivo), profiling of resistance mutations in patient-derived cell models Nature communications High 31399568
2021 ROS1 kinase domain mutations are the predominant resistance mechanism to crizotinib and lorlatinib in ROS1-positive NSCLC (identified in 38% post-crizotinib and 46% post-lorlatinib biopsies). G2032R is the most common (~1/3 of cases). A novel mutation, L2086F, was identified post-lorlatinib; structural modeling and Ba/F3 functional studies showed L2086F causes steric interference with lorlatinib, crizotinib, and entrectinib but accommodates cabozantinib, and cabozantinib produced disease control in a patient harboring L2086F. Clinical biopsy next-generation sequencing, structural modeling, Ba/F3 cell-based functional assays, clinical case report Clinical cancer research High 33685866
2021 Entrectinib acts as a dual type I/II mode ROS1 inhibitor, making it liable to both gatekeeper/solvent-front (G2032R) and type II resistance mutations. Forward mutagenesis screens identified ROS1 F2004C as a recurrent entrectinib-resistant mutation and G2032R in entrectinib- and lorlatinib-resistant clones. ROS1 L2086F is broadly resistant to all type I inhibitors but remains sensitive to type II inhibitors (e.g., cabozantinib); ROS1 F2004C/I/V are resistant to type I and type II inhibitor cabozantinib but retain sensitivity to type I macrocyclic inhibitors. Unbiased forward mutagenesis screen in Ba/F3 CD74-ROS1 and EZR-ROS1 cells, cell-based inhibitor profiling, structural modeling Molecular cancer therapeutics High 34907086

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiological reviews 4021 24987008
2020 Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nature reviews. Molecular cell biology 3586 32231263
2012 Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular signalling 3041 22286106
2016 ROS Are Good. Trends in plant science 1849 27666517
2014 Crizotinib in ROS1-rearranged non-small-cell lung cancer. The New England journal of medicine 1548 25264305
2016 ROS and ROS-Mediated Cellular Signaling. Oxidative medicine and cellular longevity 1513 26998193
2011 ROS signaling: the new wave? Trends in plant science 1394 21482172
2015 Calcium and ROS: A mutual interplay. Redox biology 1191 26296072
2012 RET, ROS1 and ALK fusions in lung cancer. Nature medicine 1068 22327623
2006 Mitochondrial ROS-induced ROS release: an update and review. Biochimica et biophysica acta 881 16829228
2018 Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell death & disease 873 29371661
2016 TNF and ROS Crosstalk in Inflammation. Trends in cell biology 803 26791157
2008 ROS and p53: a versatile partnership. Free radical biology & medicine 692 18275858
2016 Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer letters 680 27037062
2009 ROS in biotic interactions. Physiologia plantarum 525 20002601
2018 Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer discovery 408 30093503
2013 ROS production in phagocytes: why, when, and where? Journal of leukocyte biology 358 23610146
2009 Crosstalk signaling between mitochondrial Ca2+ and ROS. Frontiers in bioscience (Landmark edition) 346 19273125
2008 Aging: ROS or TOR. Cell cycle (Georgetown, Tex.) 311 18971624
2006 Localizing NADPH oxidase-derived ROS. Science's STKE : signal transduction knowledge environment 310 16926363
2013 Molecular pathways: ROS1 fusion proteins in cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 301 23719267
2007 AGE, RAGE, and ROS in diabetic nephropathy. Seminars in nephrology 293 17418682
2013 Novel targets in non-small cell lung cancer: ROS1 and RET fusions. The oncologist 284 23814043
2010 ROS signalling--specificity is required. Trends in plant science 250 20605736
2017 Mitochondrial ROS control of cancer. Seminars in cancer biology 249 28445781
2017 Oxidative toxicity in diabetes and Alzheimer's disease: mechanisms behind ROS/ RNS generation. Journal of biomedical science 248 28927401
2023 The emerging role of microplastics in systemic toxicity: Involvement of reactive oxygen species (ROS). The Science of the total environment 239 37391150
2020 ROS1-dependent cancers - biology, diagnostics and therapeutics. Nature reviews. Clinical oncology 234 32760015
2015 Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Translational lung cancer research 234 25870798
2016 Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications. Macromolecular bioscience 221 26891447
2018 Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 216 29636358
2022 Reactive Oxygen Species (ROS): Key Components in Cancer Therapies. Anti-cancer agents in medicinal chemistry 213 34102991
2016 ROS in gastrointestinal inflammation: Rescue Or Sabotage? British journal of pharmacology 213 26758851
2017 Recent Advances in Targeting ROS1 in Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 205 28818606
2017 ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer. Journal of the National Cancer Institute 201 29370427
2017 Inflammation, ROS, and Mutagenesis. Cancer cell 199 29232551
2016 Reactive Oxygen Species (ROS): Beneficial Companions of Plants' Developmental Processes. Frontiers in plant science 186 27729914
1987 Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proceedings of the National Academy of Sciences of the United States of America 183 2827175
2008 Mechanisms of ROS modulated cell survival during carcinogenesis. Cancer letters 182 18372105
2016 ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours. Histopathology 181 26647767
2016 Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Archiv : an international journal of pathology 170 27535289
2019 RGF1 controls root meristem size through ROS signalling. Nature 165 31801996
2017 Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise. Journal of physiology and biochemistry 162 28707280
2023 Multifunctional PtCuTe Nanosheets with Strong ROS Scavenging and ROS-Independent Antibacterial Properties Promote Diabetic Wound Healing. Advanced materials (Deerfield Beach, Fla.) 156 37723937
2017 ROS-induced ROS release in plant and animal cells. Free radical biology & medicine 151 29203327
2014 Biomarkers That Currently Affect Clinical Practice in Lung Cancer: EGFR, ALK, MET, ROS-1, and KRAS. Frontiers in oncology 137 25157335
2016 Endogenous mechanisms of reactive oxygen species (ROS) generation. Postepy higieny i medycyny doswiadczalnej (Online) 134 27892899
1986 Characterization of an activated human ros gene. Molecular and cellular biology 134 3785223
2011 ROS-induced ROS release in vascular biology: redox-redox signaling. American journal of physiology. Heart and circulatory physiology 129 21685266
2008 Autoimmune thyroiditis and ROS. Autoimmunity reviews 125 18625441
2019 The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nature communications 123 31399568
2021 Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 120 33685866
2016 SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 118 27540894
2012 ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert review of anticancer therapy 118 22500682
2014 Mitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator. Mitochondrion 117 24954615
2017 ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. Pharmacological research 111 28465216
2015 Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert opinion on investigational drugs 110 26457764
2022 ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date. Current oncology (Toronto, Ont.) 104 35200557
2016 The ROS Wheel: Refining ROS Transcriptional Footprints. Plant physiology 103 27246095
2014 Optogenetic control of ROS production. Redox biology 103 24563855
2018 E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. Cancer discovery 99 29610289
1991 Transient and locally restricted expression of the ros1 protooncogene during mouse development. The EMBO journal 96 1718742
2015 Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proceedings of the National Academy of Sciences of the United States of America 91 26372962
2011 Sirt3, mitochondrial ROS, ageing, and carcinogenesis. International journal of molecular sciences 89 22016654
2019 Reactive Oxygen Species (ROS), Intimal Thickening, and Subclinical Atherosclerotic Disease. Frontiers in cardiovascular medicine 88 31428618
2016 ROS and intracellular ion channels. Cell calcium 87 26995054
2021 Reactive oxygen species (ROS): utilizing injectable antioxidative hydrogels and ROS-producing therapies to manage the double-edged sword. Journal of materials chemistry. B 78 34304256
2017 Extracellular acidification induces ROS- and mPTP-mediated death in HEK293 cells. Redox biology 74 29331741
2015 Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 74 25612511
2021 Reactive oxygen species (ROS): Critical roles in breast tumor microenvironment. Critical reviews in oncology/hematology 71 33716202
2014 TRPs as chemosensors (ROS, RNS, RCS, gasotransmitters). Handbook of experimental pharmacology 68 24961969
2016 ROS1 fusions in cancer: a review. Future oncology (London, England) 66 27256160
2014 Mitochondria in ageing: there is metabolism beyond the ROS. FEMS yeast research 64 24373480
2022 Reactive Oxygen Species (ROS) and Antioxidants as Immunomodulators in Exercise: Implications for Heme Oxygenase and Bilirubin. Antioxidants (Basel, Switzerland) 63 35204062
2021 Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer. Cancer treatment reviews 60 33743408
2017 Reciprocity in ROS and autophagic signaling. Current opinion in toxicology 59 29457143
2018 ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 58 30543838
2015 McMYB10 regulates coloration via activating McF3'H and later structural genes in ever-red leaf crabapple. Plant biotechnology journal 57 25641214
2016 ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare. Lung cancer (Amsterdam, Netherlands) 55 26973202
2018 Catalase inhibition induces pexophagy through ROS accumulation. Biochemical and biophysical research communications 54 29753736
2023 Crosstalk between G-quadruplex and ROS. Cell death & disease 52 36653351
2019 ROS1-Dependent DNA Demethylation Is Required for ABA-Inducible NIC3 Expression. Plant physiology 52 30692220
1987 Human ros1 and mas1 oncogenes located in regions of chromosome 6 associated with tumor-specific rearrangements. Oncogene research 51 3329713
2023 PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS. Autophagy 50 36541703
2021 Metformin Attenuates ROS via FOXO3 Activation in Immune Cells. Frontiers in immunology 44 33953705
2019 Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer. Cancer chemotherapy and pharmacology 42 31256210
2020 New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Current oncology reports 41 32296961
2017 ALK and ROS1 testing on lung cancer cytologic samples: Perspectives. Cancer cytopathology 40 28743163
2012 Plant cell division: ROS homeostasis is required. Plant signaling & behavior 40 22751303
2021 ROS as Regulators of Cellular Processes in Melanoma. Oxidative medicine and cellular longevity 38 34725562
2025 Taletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 37 40179330
2014 Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1. The Journal of clinical investigation 37 25401476
2021 Entrectinib: A Review in NTRK+ Solid Tumours and ROS1+ NSCLC. Drugs 36 33871816
2021 ROS1 Targeted Therapies: Current Status. Current oncology reports 36 34125313
2021 Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors. Molecular cancer therapeutics 35 34907086
2020 Clinical, morphologic, and genomic findings in ROS1 fusion Spitz neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 34 32862201
2014 Genetically encoded reactive oxygen species (ROS) and redox indicators. Biotechnology journal 31 24497389
2023 Molecular basis of the plant ROS1-mediated active DNA demethylation. Nature plants 29 36624257
2013 ALK and ROS1 as a joint target for the treatment of lung cancer: a review. Translational lung cancer research 29 25806218
2020 Reactive Oxygen Species (ROS) and Nucleic Acid Modifications During Seed Dormancy. Plants (Basel, Switzerland) 28 32471221

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