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BIOMARKER:

ROS1 wild-type

i
Other names: ROS1, ROS Proto-Oncogene 1 Receptor Tyrosine Kinase, V-Ros Avian UR2 Sarcoma Virus Oncogene Homolog 1, C-Ros Oncogene 1 Receptor Tyrosine Kinase, Proto-Oncogene Tyrosine-Protein Kinase ROS, Proto-Oncogene C-Ros-1, MCF3, ROS, V-Ros UR2 Sarcoma Virus Oncogene Homolog 1 (Avian), ROS Proto-Oncogene 1 Receptor Tyrosine Kinase, Transmembrane Tyrosine-Specific Protein Kinase, Receptor Tyrosine Kinase C-Ros Oncogene 1, C-Ros Receptor Tyrosine Kinase, Proto-oncogene C-Ros, C-Ros-1
Entrez ID:
2ms
Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: a drug evaluation of phase I and II data. (PubMed, Expert Opin Investig Drugs)
While crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC), unmet needs remain. Taltrectinib has the potential to improve PFS based on its greater potency against ROS1+ tumors and high CNS penetration. By selectively inhibiting ROS1 wild-type and its resistant mutations over TRKB, taltrectinib has a better safety profile with minimal CNS-related AEs compared to other ROS1+ inhibitors.
P1 data • Review • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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ROS1 fusion • ROS1 positive • ROS1 wild-type
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • taletrectinib (AB-106)
3ms
KLC1-ROS1 Fusion Exerts Oncogenic Properties of Glioma Cells via Specific Activation of JAK-STAT Pathway. (PubMed, Cancers (Basel))
Combination treatment with the chemotherapeutic agent temozolomide and an inhibitor of ROS1, JAK2, or a downstream target of STAT3, demonstrated antitumor effects against KLC1-ROS1 fusion-expressing glioma cells. Our results demonstrate that KLC1-ROS1 fusion exerts oncogenic activity through serum-independent constitutive activation, resulting in specific activation of the JAK-STAT pathway. Our data suggested that molecules other than RTKs may serve as novel therapeutic targets for RTK fusion in gliomas.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • KLC1 (Kinesin light chain 1)
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ROS1 fusion • ROS1 wild-type • KLC1-ROS1 fusion
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temozolomide
5ms
Induction Chemo-Nivo in Unresectable Stage III NSCLC (clinicaltrials.gov)
P2, N=37, Recruiting, Ralph G Zinner | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy • Surgery
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK wild-type • ROS1 wild-type
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Opdivo (nivolumab) • paclitaxel • docetaxel
7ms
New P2 trial • Combination therapy • Surgery
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK wild-type • ROS1 wild-type
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Opdivo (nivolumab) • paclitaxel • docetaxel
8ms
ROS1 mutations as potential negative predictor for response of immunotherapy in patient with head and neck cancer (ESMO 2023)
Conclusions We identified that ROS1 mutation predicted the resistance to ICIs in HNSCs. The clinical delivery of ICIs should be cautious in those patients.
Clinical • IO biomarker
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TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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TMB-H • ROS1 rearrangement • ROS1 mutation • ROS1 wild-type
8ms
LIPI-based Score Predicting OS Benefit for the Addition of Chemotherapy to Pembrolizumab in aNSCLC with PD-L1 TPS≥50% (IASLC-WCLC 2023)
With the limitations of the retrospective analysis, the proposed LIPI-based score seems to predict OS with P and PCT. Prospective validation is required.
PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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LDH elevation • ALK wild-type • ROS1 wild-type
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Keytruda (pembrolizumab)
11ms
First-Line Treatment of Driver-Negative Non-Small Cell Lung Cancer. (PubMed, Hematol Oncol Clin North Am)
This article summarizes the most up-to-date trial data on treatments for driver-negative advanced non-small cell lung cancer, including immunotherapy monotherapy, chemoimmunotherapy, and combination immunotherapy, providing a framework for clinicians based on PD-L1 and smoking status. A multibiomarker assay that may best predict immunotherapy response remains an active area of research.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
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ROS1 wild-type • EGFR negative
11ms
Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC (clinicaltrials.gov)
P2, N=42, Recruiting, Georgetown University | Trial primary completion date: Jul 2023 --> Jul 2024
Trial primary completion date • Metastases
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • ALK wild-type • ROS1 wild-type
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Avastin (bevacizumab) • Tecentriq (atezolizumab) • tiragolumab (RG6058)
11ms
Natural history and treatment efficacy in an ambispective case series of NTRK-rearranged mesenchymal tumors. (PubMed, ESMO Open)
Our study confirms low frequency and histotype diversity of NTRK fusion in STS. While the activity of TRKi in simple genomics NMT is confirmed, our clinical data encourage subsequent studies focusing on the biological relevance of NTRK fusions in sarcomas with complex genomics together with the efficacy of TRKi in this population.
Retrospective data • Journal
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ALK (Anaplastic lymphoma kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
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ALK rearrangement • ROS1 wild-type • NTRK fusion
over1year
PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer - A Pilot Study (clinicaltrials.gov)
P1, N=40, Recruiting, Peter MacCallum Cancer Centre, Australia | Initiation date: Oct 2022 --> Jan 2022
Trial initiation date • Metastases
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EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK wild-type • ROS1 wild-type
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Keytruda (pembrolizumab) • carboplatin • paclitaxel
over1year
Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma. (PubMed, Cancer Genomics Proteomics)
We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 fusion • ROS1 wild-type
over1year
ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer. (PubMed, Int J Cancer)
Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response...In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EPHA6 (EPH Receptor A6) • MCM9 (Minichromosome Maintenance 9 Homologous Recombination Repair Factor) • SRPK1 (SRSF Protein Kinase 1)
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KRAS mutation • ROS1 fusion • ROS1 rearrangement • KRAS Q61H • ROS1 wild-type
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Xalkori (crizotinib)
over1year
PRIME_LUNG: Primary Radiotherapy In MEtastatic Lung Cancer - A Pilot Study (clinicaltrials.gov)
P1, N=40, Recruiting, Peter MacCallum Cancer Centre, Australia | Not yet recruiting --> Recruiting | Initiation date: Apr 2022 --> Oct 2022
Enrollment open • Trial initiation date • Metastases
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EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK wild-type • ROS1 wild-type
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Keytruda (pembrolizumab) • carboplatin • paclitaxel
over1year
New P2 trial
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EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK wild-type • ROS1 wild-type
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Focus V (anlotinib) • Anniko (penpulimab)
over2years
Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC (clinicaltrials.gov)
P2; N=42; Recruiting; Sponsor: Georgetown University; Not yet recruiting ➔ Recruiting
Enrollment open • Clinical
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • ALK wild-type • ROS1 wild-type
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Avastin (bevacizumab) • Tecentriq (atezolizumab) • tiragolumab (RG6058)