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BIOMARKER:

ROS1 rearrangement

i
Entrez ID:
7d
Real-world studies of crizotinib in patients with ROS1-positive non-small-cell lung cancer: experience from China. (PubMed, J Comp Eff Res)
However, due to the paucity of solid data from randomized, controlled phase III clinical studies, clinicians often require more systematic, real-world data-based guidance for its optimal clinical use. As one of the leading countries of real-world research on crizotinib, China has contributed significantly to data on standardization of the therapeutic use of crizotinib, including its clinical treatment patterns, the timing and duration of treatment and drug resistance monitoring and management.
Review • Journal • Real-world evidence • Real-world
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 positive • ROS1 rearrangement
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Xalkori (crizotinib)
16d
Partial Response to Treatment with ALK Inhibitor in a Patient With SQSTM1-ALK Fusion Positive Lung Adenocarcinoma. (PubMed, Eur J Case Rep Intern Med)
Recognition of rare ALK fusions This case highlights the importance of identifying rare ALK fusions, such as SQSTM1-ALK, in non-small cell lung cancer (NSCLC), which can guide personalised treatment strategies.Utility of advanced molecular diagnostics The use of next-generation sequencing alongside immunohistochemistry is crucial for accurately detecting ALK and ROS1 rearrangements, avoiding false positives and enabling the identification of druggable mutations.Impact of personalised medicine This case reinforces the value of personalised medicine in NSCLC, where molecular profiling can uncover unique genetic alterations, allowing for more tailored and potentially more effective treatments.
Journal • PD(L)-1 Biomarker
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PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SQSTM1 (Sequestosome 1)
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PD-L1 expression • ALK positive • ALK rearrangement • ALK fusion • ROS1 positive • ROS1 rearrangement
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Alecensa (alectinib)
21d
Histiocyte-rich ROS1-rearranged inflammatory myofibroblastic tumour of the trachea: A rare neoplasm presenting with asthma-like symptoms. (PubMed, Respirol Case Rep)
The patient presented with upper airway obstruction, which was an asthma mimic. The tumour demonstrated rapid recurrence after mechanical coring, which subsequently controlled with radiotherapy.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
23d
AVANZAR: Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations (clinicaltrials.gov)
P3, N=1350, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: Feb 2027 --> Nov 2027 | Trial primary completion date: Feb 2027 --> Nov 2027
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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EGFR mutation • ALK rearrangement • ROS1 rearrangement • TROP2 positive
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Keytruda (pembrolizumab) • cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a)
28d
DB-1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026
Enrollment change • Trial completion date • Trial primary completion date • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD276 (CD276 Molecule)
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BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • NTRK1 mutation
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BNT324
1m
Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer. (PubMed, Onco Targets Ther)
Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.
Review • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 mutation • RET fusion • ALK rearrangement • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • NRG1 fusion • KRAS G12 • NRG1 fusion • NTRK fusion
1m
Young-Onset, ROS1-Rearranged Adenocarcinoma of the Lung With Cardiac Tamponade: A Case Report. (PubMed, Cureus)
Oral administration of entrectinib was highly effective, and his serum carcinoembryonic antigen (CEA) level improved from 247 to 10.8 ng/mL. The present case has clinical significance because a pathological and genetic diagnosis was made from the pericardial effusion fluid, and the clinical manifestations of cardiac tamponade due to lung cancer were well controlled by the administration of entrectinib.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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ROS1 rearrangement
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Rozlytrek (entrectinib)
2ms
Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer. (PubMed, Clin Transl Med)
The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.
Review • Journal
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 fusion • ROS1 positive • ROS1 rearrangement • ROS1 G2032R
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
Response to Crizotinib After Entrectinib Resistance in ROS1-Rearranged, MET-Amplified Lung Adenocarcinoma. (PubMed, JCO Precis Oncol)
Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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MET amplification • ROS1 rearrangement • ROS1 amplification
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Xalkori (crizotinib) • Rozlytrek (entrectinib)
3ms
Exceptional long term response to crizotinib in ROS 1-postive advanced non small cell lung cancer. (PubMed, Respirol Case Rep)
Despite the initial poor response to conventional chemotherapy, the patient exhibited an exceptional and sustained response to crizotinib, with a progression-free survival of 94 months and complete metabolic response on PET scan. This case underscores the importance of molecular profiling in guiding treatment decisions and highlights the efficacy of targeted therapies for ROS1-positive NSCLC.
Journal • Metastases
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 fusion • ROS1 positive • ROS1 rearrangement
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Xalkori (crizotinib)
3ms
Molecular diagnostic characteristics in non-small cell lung carcinomas (NSCLC) and its relationship with the PD-L1 expression (ECP 2024)
Our study showed the heterogeneity in PD-L1 expression with respect to major oncogenic drivers in Turkey. KRAS, BRAF, MET mutations and ALK and ROS1 rearrangements were more frequent, while EGFR and HER2 mutations were less frequent compared with the overall PD-L1 expression levels. Molecular testing of non-small cell lung carcinomas (NSCLC) for oncogenic driver mutations has become standard in pathology practice.
PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • PD-L1 underexpression • ALK rearrangement • MET exon 14 mutation • PD-L1 negative • ROS1 rearrangement • MET mutation
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VENTANA PD-L1 (SP263) Assay
3ms
ROS1-rearranged non-small cell lung cancer: Understanding biology and optimizing management in the era of new approvals. (PubMed, Curr Probl Cancer)
Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.
Review • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
4ms
Unusual presentation of ROS1 rearranged metastatic non-small cell lung cancer. (PubMed, Respir Med Case Rep)
The patient was ultimately diagnosed with ROS1 rearranged lung adenocarcinoma and achieved a dramatic response with entrectinib. This case highlights the variable presentation of non-small cell lung cancer (NSCLC) and the importance of comprehensive molecular testing for newly diagnosed metastatic NSCLC.
Journal • Metastases
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Rozlytrek (entrectinib)
5ms
Reciprocal DNA Fusions and their Association with DNA Damage Response Genes in Patients with NSCLC Through cfDNA NGS (IASLC-WCLC 2024)
Notably, individuals with exclusive reciprocal rearrangements of RET or ROS1 might be less prone to co-mutations in TP53, ATM, and ARID1A, than are those with detectable activating rearrangements. This emphasizes the significance of evaluating co-mutations in DNA repair genes alongside fusions to refine treatment approaches.
Clinical • BRCA Biomarker • Next-generation sequencing • Cell-free DNA
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ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1)
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TP53 mutation • BRCA1 mutation • ATM mutation • ALK rearrangement • ARID1A mutation • ALK fusion • ROS1 rearrangement • RET rearrangement
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Guardant360® CDx
8ms
Immunotherapy for patients with advanced non-small cell lung cancer harboring oncogenic driver alterations other than EGFR: a multicenter real-world analysis. (PubMed, Transl Lung Cancer Res)
For NSCLC with ALK, RET and ROS1 rearrangement, MET exon 14 skipping mutation, or BRAF V600E mutation, effectiveness of single or combined ICI therapy remains limited, therefore, targeted therapies should be considered prior to immunotherapy regimens. Future studies should address the investigation of better predictive biomarkers for immunotherapy response in oncogene-driven NSCLC.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • BRAF V600E • KRAS mutation • BRAF V600 • ALK positive • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • RET rearrangement
8ms
PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov)
P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases • Immuno-oncology
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • ALK rearrangement • ROS1 rearrangement
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Imfinzi (durvalumab) • docetaxel • Orpathys (savolitinib) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • monalizumab (IPH2201)
8ms
IOSI-LUNG-001: Atezolizumab Plus 8 Gy Single-fraction Radiotherapy for Advanced Oligoprogressive NSCLC (clinicaltrials.gov)
P2, N=12, Active, not recruiting, Oncology Institute of Southern Switzerland | Recruiting --> Active, not recruiting | N=20 --> 12 | Trial completion date: Dec 2022 --> Dec 2024
Enrollment closed • Enrollment change • Trial completion date • Metastases
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK fusion • ROS1 rearrangement
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Tecentriq (atezolizumab)
8ms
Reclassification of a spindle cell sarcoma after identification of a TFG-ROS1 fusion: A case demonstrating the clinical benefit of next-generation sequencing in sarcoma. (PubMed, Mol Genet Genomic Med)
We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK-negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.
Journal • Next-generation sequencing
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD34 (CD34 molecule) • SOX10 (SRY-Box 10) • USP6 (Ubiquitin Specific Peptidase 6)
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ALK rearrangement • ALK fusion • ROS1 fusion • ROS1 rearrangement • ALK negative • TFG-ROS1 rearrangement
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Xalkori (crizotinib)
9ms
Lung adenocarcinoma patients with ROS1-rearranged tumors by sex and smoking intensity. (PubMed, Heliyon)
Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.
Journal
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib)
9ms
Genomic testing and targeted therapy of non-small cell lung cancer in China: a nationwide survey of physicians and clinical pathologists. (PubMed, Ann Palliat Med)
The improvement of the non-tertiary hospital pathology departments' detection capabilities and the physicians' awareness are needed for enhancing the rate of genomic testing and targeted therapy in NSCLC patients in China.
Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • ALK rearrangement • ROS1 fusion • ROS1 rearrangement
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Xalkori (crizotinib) • gefitinib
10ms
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. (PubMed, J Transl Med)
In this study we knock-in for the first time in a ROS1 + patient-derived cell line, three different known resistance-causing mutations using CRISPR/Cas9 in the endogenous translocated ROS1 alleles. Pharmacological assays performed in 2D and 3D cell culture revealed that spheroids are more sensitive to TKIs than cells cultured as a monolayer. This direct comparison between two culture systems could be done thanks to the implementation of normalized growth rates (NGR) to uniformly quantify drug response between 2D and 3D cell culture. Overall, this study presents the added value of using spheroids and positions lorlatinib and repotrectinib as the most effective TKIs against the studied ROS1 resistance point mutations.
Preclinical • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SLC34A2 (Solute carrier family 34 member 2)
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ROS1 rearrangement • ROS1 G2032R • ROS1 S1986Y
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Augtyro (repotrectinib)
10ms
Real-world data analysis of comprehensive genomic profiling using plasma samples from non-small cell lung cancer patients (AACR 2024)
In patients without known driver oncogenes, mutations associated with approved therapeutic implications were detected in 12.0%. The detection of gene rearrangements using liquid biopsy may be limited compared with genetic mutations.
Real-world evidence • Clinical • Real-world
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • ALK rearrangement • MET exon 14 mutation • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • KRAS G12
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FoundationOne® Liquid CDx
10ms
Kinase Fusions in Spitz Melanocytic Tumors: The Past, the Present, and the Future. (PubMed, Dermatopathology (Basel))
The knowledge of molecular drivers is of great interest in the field of melanocytic diagnostics, and it is important to consider that in addition to immunohistochemistry, molecular techniques such as FISH, PCR, and/or NGS are essential to confirm and classify the different patterns of mutation. Future studies with large case series and molecular sequencing techniques are needed to allow for a more complete and comprehensive understanding of the role of fusion kinases in the spitzoid tumor family.
Review • Journal
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)
|
ALK rearrangement • ALK fusion • ROS1 fusion • ROS1 rearrangement
10ms
Enrollment change
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PD-L1 (Programmed death ligand 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • LAG3 (Lymphocyte Activating 3)
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PD-L1 expression • ROS1 rearrangement • LAG3 expression
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carboplatin • albumin-bound paclitaxel • Hetronifly (serplulimab) • HLX26
10ms
LUN 17-139: Phase II Randomized Trial of Carboplatin+Pemetrexed+Bevacizumab+/- Atezolizumab in Stage IV NSCLC (clinicaltrials.gov)
P2, N=117, Recruiting, Fox Chase Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • ALK rearrangement • EGFR exon 21 mutation • ROS1 rearrangement • EGFR exon 18 mutation
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • pemetrexed
10ms
MGD019 DART® Protein in Unresectable/Metastatic Cancer (clinicaltrials.gov)
P1, N=162, Active, not recruiting, MacroGenics | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Jul 2024
Trial completion date • Trial primary completion date • Metastases
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • BRAF mutation • EGFR T790M • ALK rearrangement • ROS1 rearrangement
|
lorigerlimab (MGD019)
10ms
Randomized Study of Stereotactic Body Radiation Therapy (SBRT) in Patients With Oligoprogressive Metastatic Cancers of the Breast and Lung (clinicaltrials.gov)
P2, N=107, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK rearrangement • ROS1 rearrangement
11ms
Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial. (PubMed, ESMO Open)
Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.
Journal
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TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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TP53 mutation • ROS1 fusion • ROS1 positive • ROS1 rearrangement
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Xalkori (crizotinib)
11ms
Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer. (PubMed, Cancers (Basel))
These findings confirm crizotinib's sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.
Journal • Real-world evidence • Real-world • Metastases
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KRAS (KRAS proto-oncogene GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD74 (CD74 Molecule)
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KRAS mutation • KRAS G12D • ROS1 fusion • ROS1 rearrangement • KRAS G12 • ROS1 G2032R • ROS1 D2033N
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Xalkori (crizotinib)
12ms
From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC). (PubMed, Diagnostics (Basel))
The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood-brain barrier penetration are the reasons for the growing popularity and interest in this molecule. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK rearrangement • ROS1 positive • ROS1 rearrangement
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
12ms
Progress of non-small-cell lung cancer with ROS1 rearrangement. (PubMed, Front Mol Biosci)
Tyrosine kinase inhibitors (TKIs) target ROS1 and can block tumor growth and provide clinical benefits to patients. This review summarizes the current knowledge on ROS1 rearrangements in NSCLCs, including the mechanisms of ROS1 oncogenicity, epidemiology of ROS1-positive tumors, methods for detecting rearrangements, molecular characteristics, therapeutic agents, and mechanisms of drug resistance.
Review • Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ROS1 positive • ROS1 rearrangement
12ms
In-depth Analysis of Lorlatinib-related neurocognitive Adverse Events in Patients With Non-small-cell Lung Cancer. (PubMed, Clin Lung Cancer)
Lorlatinib treatment did not result in a sustained and significant decline within any of the specified neurocognitive domains.
Journal • Adverse events
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK rearrangement • ROS1 rearrangement
|
Lorbrena (lorlatinib)
12ms
Case report: Successful sequential therapy of crizotinb and entrectinib in ROS1-positive non-small-cell lung cancer with brain metastasis in later-settings. (PubMed, Medicine (Baltimore))
A ROS1-rearranged NSCLC with CNS metastases responded to sequential tyrosine kinase inhibitors treatment of crizotinb followed by entrectinib. This report has potential implications in guiding decisions for the treatment after crizotinib resistance.
Journal • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
|
NTRK2 fusion • ALK fusion • ALK mutation • ROS1 fusion • ROS1 positive • ROS1 rearrangement
|
Opdivo (nivolumab) • Avastin (bevacizumab) • Xalkori (crizotinib) • Rozlytrek (entrectinib) • paclitaxel • Focus V (anlotinib)
1year
Phase I/II Study of Nivolumab and Ipilimumab Combined With Nintedanib in Non Small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=68, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2024
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • ALK rearrangement • ROS1 rearrangement
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • nintedanib
1year
Comprehensive molecular analysis of driver mutations in non-small cell lung carcinomas and its correlation with PD-L1 expression, An Indian perspective. (PubMed, Pathol Res Pract)
This is one of the largest cohorts of NSCLC for comprehensive targeted mutational profiling and correlation with the PD-L1 expression. The mutations are more prevalent in non-smoker females for all genes, except ALK (non-smoker males). MET and BRAF mutations are more common in elderly population whereas EGFR mutations, and ALK and ROS1 genes rearrangements are more prevalent in younger population. The most common histopathologic subtype/feature associated with various mutations was as follows: acinar with EGFR, solid with ALK, macronucleoli with ROS1, signet ring with MET, and micropapillary with BRAF.
Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • ALK rearrangement • MET exon 14 mutation • PD-L1 negative • EGFR L861Q • ALK mutation • ROS1 rearrangement • EGFR G719X • MET mutation • EGFR S768I
1year
Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants. (PubMed, Thorac Cancer)
The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same.
Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SDC4 (Syndecan 4)
|
ROS1 fusion • ROS1 positive • ROS1 rearrangement • SDC4-ROS1 fusion
|
Xalkori (crizotinib)
1year
CD74/SLC34A2-ROS1 fusion variants involving the transmembrane region predict poor response to crizotinib in non-small cell lung cancer independent of TP53 mutations. (PubMed, J Thorac Oncol)
Long CD74/SLC34A2-ROS1 fusions, which retain transmembrane regions in ROS1 and fusion partners, are associated with poor response to crizotinib independent of TP53 mutations.
Journal
|
TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD74 (CD74 Molecule) • SLC34A2 (Solute carrier family 34 member 2) • TPM3 (Tropomyosin 3) • SDC4 (Syndecan 4)
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TP53 mutation • ROS1 fusion • ROS1 rearrangement • SDC4-ROS1 fusion • BCL2L11 deletion • SLC34A2-ROS1 fusion
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Xalkori (crizotinib)
1year
Concordance of Immunohistochemistry and Fluorescence In Situ Hybridization in the Detection of Anaplastic Lymphoma Kinase (ALK) and Ros Proto-oncogene 1 (ROS1) Gene Rearrangements in Non-Small Cell Lung Carcinoma: A 4.5-Year Experience Highlighting Challenges and Pitfalls. (PubMed, Arch Pathol Lab Med)
Immunostaining is a robust method for ALK-rearrangement testing, with fluorescence in situ hybridization adding value in the rare equivocal stained case. ROS1-rearrangement testing is more cost-effective if immunohistochemistry is followed by fluorescence in situ hybridization after excluding EGFR-mutant and ALK-rearranged adenocarcinomas.
Journal • Discordant
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK rearrangement • ROS1 positive • ROS1 rearrangement
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VENTANA ALK (D5F3) CDx Assay
1year
A Study of SI-B001+SI-B003± Chemotherapy in the Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=160, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting | Trial completion date: Aug 2025 --> Nov 2025 | Initiation date: Aug 2023 --> Oct 2023 | Trial primary completion date: Aug 2025 --> Nov 2025
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF mutation • BRAF V600 • EGFR wild-type • MET exon 14 mutation • ALK fusion • RET mutation • ROS1 fusion • ROS1 rearrangement • RET rearrangement • NTRK fusion
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izalontamab (SI-B001) • danvilostomig (SI-B003)
1year
Enrollment open
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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 rearrangement • PD-L1 negative • ROS1 rearrangement
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Keytruda (pembrolizumab) • carboplatin • paclitaxel • pemetrexed • volrustomig (MEDI5752)
1year
Repotrectinib's Clinical Benefit and Its Brain Penetration in a Patient with Meningeal Carcinomatosis from G2032R-Mutated ROS-1 Positive Non-Small Cell Lung Cancer. (PubMed, Oncol Ther)
In line with its activity, we documented the presence of the drug at potentially active concentrations in the cerebrospinal fluid. Nevertheless, the short-lived response reported by our patient highlights the importance for novel ROS1-tyrosine kinase inhibitors (TKIs) to be specifically developed to be able to penetrate the blood-brain barrier.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 positive • ROS1 rearrangement • ROS1 G2032R
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Augtyro (repotrectinib)
1year
MGD019 DART® Protein in Unresectable/Metastatic Cancer (clinicaltrials.gov)
P1, N=162, Active, not recruiting, MacroGenics | Trial completion date: Apr 2024 --> Sep 2024 | Trial primary completion date: Oct 2023 --> Mar 2024
Trial completion date • Trial primary completion date • Metastases
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • BRAF mutation • EGFR T790M • ALK rearrangement • ROS1 rearrangement
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lorigerlimab (MGD019)