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    GENE:

    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

    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
    14h
    Development of the serotonin release assay with enterochromaffin cell-rich human intestinal organoids for the risk evaluation of drug-induced emesis. (PubMed, Toxicol Sci)
    Epidermal growth factor receptor (EGFR) TKIs exhibit a lower potency for inducing 5-HT release, which is consistent with their low emetic risk. In summary, the use of EC cell-rich organoids in 5-HT release assays may prove to be a valuable tool in predicting drug-induced emesis in humans during the drug development.
    Journal
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    19h
    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
    |
    Xalkori (crizotinib)
    20h
    PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma. (PubMed, J Clin Med)
    The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • ATM mutation • PIK3CA H1047R • PTEN mutation • PIK3CA E545K • CDKN2A mutation • SMARCA4 mutation • PIK3CA E545 • PIK3CA E542
    21h
    Lung Cancer with Brain Metastasis-Treatment Strategies and Molecular Characteristics. (PubMed, J Clin Med)
    Immunotherapies, alone or in combination with other treatments, have demonstrated promising results in NSCLC with BMs, although most clinical trials have included only selected patients with asymptomatic or previously treated BMs. In this review, we discuss the molecular and immune characteristics of NSCLC with BMs, analyze intracranial efficacy findings from clinical trials, and explore treatment strategies for lung cancer patients with BMs.
    Review • Journal • IO biomarker
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    1d
    Bisulfite-Free and Quantitative Detection of DNA Methylation at Single-Base Resolution by eROS1-seq. (PubMed, Anal Chem)
    Using eROS1-seq, we successfully achieved quantitative and site-specific detection of 5mC in the genomic DNA of lung cancer tissue. Overall, the eROS1-seq approach is bisulfite-free and straightforward, making it a valuable tool for the quantitative detection of 5mC at single-base resolution.
    Journal • Epigenetic controller
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    6d
    A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001) (clinicaltrials.gov)
    P1, N=230, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MGMT (6-O-methylguanine-DNA methyltransferase)
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    Keytruda (pembrolizumab) • carboplatin • gemcitabine • albumin-bound paclitaxel • pemetrexed • MK-0482
    6d
    Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1. (PubMed, Front Oncol)
    This study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    BRAF mutation • ALK mutation
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    TruSight Oncology 500 Assay
    8d
    Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC (clinicaltrials.gov)
    P1/2, N=20, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Feb 2026 --> Jan 2025
    Trial primary completion date • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD4 (CD4 Molecule)
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    Opdivo (nivolumab) • cyclophosphamide • fludarabine IV
    9d
    APPEAL: APatinib Plus Chemotherapy vErsus Chemotherapy As First-line Treatment for Advanced NSCLC (clinicaltrials.gov)
    P2, N=0, Withdrawn, Sun Yat-sen University | N=128 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Metastases
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK rearrangement
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    carboplatin • AiTan (rivoceranib) • pemetrexed
    9d
    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)
    |
    PD-L1 expression • ALK positive • ALK rearrangement • ALK fusion • ROS1 positive • ROS1 rearrangement
    |
    Alecensa (alectinib)
    9d
    Repotrectinib: a promising new therapy for advanced nonsmall cell lung cancer. (PubMed, Ann Med Surg (Lond))
    Notably, the phase 1/2 TRIDENT-1 study showed impressive progression-free survival and intracranial activity in both TKI-naïve and pretreated patients. With its high response rates and manageable side effects, repotrectinib is set to play a significant role in treating ROS1+ and NTRK+advanced solid tumors, highlighting the ongoing need for research and clinical application.
    Review • Journal • Metastases
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ROS1 positive • NTRK positive
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    Augtyro (repotrectinib)
    9d
    MP-VAC-205: Vactosertib in Combination with Pembrolizumab for PD-L1 Positive Non-small Cell Lung Cancer (NSCLC) Subjects (clinicaltrials.gov)
    P2, N=11, Terminated, MedPacto, Inc. | N=55 --> 11 | Trial completion date: Dec 2025 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2022 --> Aug 2024; This is because Medpacto decided to modify its development strategy as the business and development environment changed.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression
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    PD-L1 IHC 22C3 pharmDx
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    Keytruda (pembrolizumab) • vactosertib (TEW-7197)
    13d
    Association of pre-existing conditions with major driver mutations and PD-L1 expression in NSCLC. (PubMed, BMJ Open Respir Res)
    This large-scale, cross-sectional study reveals a complex interplay between genetic mutations, immunological features and pre-existing conditions in NSCLC patients, offering insights that could inform personalised treatment strategies.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression • EGFR mutation • BRAF mutation • EGFR L858R • EGFR exon 19 deletion • ROS1 mutation
    13d
    Crizotinib Associated Renal Abscess --A Case Report- (PubMed, Hinyokika Kiyo)
    Her blood test showed a high c-reactive protein (CRP) levels ; therefore, she was admitted and received levofloxacin drip infusion for 5 days. Pathology of the left kidney revealed a renal abscess, but there was no sign of malignancy. Crizotinib has been reported to cause rare adverse effects, such as polycystic renal lesions or renal abscesses.
    Journal
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CRP (C-reactive protein)
    |
    ROS1 mutation
    |
    Xalkori (crizotinib)
    13d
    A Trial of Sintilimab Plus Anlotinib For Metastatic NSCLC After First-Line PD-1 Inhibitor (clinicaltrials.gov)
    P2, N=29, Completed, Zhejiang Cancer Hospital | Recruiting --> Completed | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Sep 2024
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    Focus V (anlotinib) • Tyvyt (sintilimab)
    13d
    CORAL-Lung: Concomitant Radiotherapy, Tremelimumab & Durvalumab for Advanced NSCLC Patients Progressing on First-line Immunotherapy (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sheba Medical Center | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK rearrangement • ALK translocation
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab)
    14d
    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)
    |
    ROS1 rearrangement
    16d
    A Clinical Trial of TG6050 in Patients With Metastatic Non-Small Cell Lung Cancer (Delivir) (clinicaltrials.gov)
    P1, N=36, Recruiting, Transgene | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • BRAF V600 • HER-2 mutation • RET fusion • RET mutation • ROS1 fusion • RET rearrangement • KRAS G12
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    TG6050
    16d
    Receptor tyrosine kinase fusion-mediated resistance to EGFR-TKI in EGFR-mutant NSCLC: a multi-center analysis and literature review. (PubMed, J Thorac Oncol)
    Emergence of RTK fusions is one of the mechanisms of bypass resistance of EGFR TKI. Dual inhibition of EGFR-RTK was safe and efficacious in patients with targetable RTK fusion post progression on EGFR TKIs.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • RET fusion • ALK fusion • ROS1 fusion
    17d
    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
    |
    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)
    |
    EGFR mutation • ALK rearrangement • ROS1 rearrangement • TROP2 positive
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • Imfinzi (durvalumab) • paclitaxel • pemetrexed • datopotamab deruxtecan (DS-1062a)
    19d
    LUNG-MAP Sub-Study: Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=124, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    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) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR T790M • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation
    |
    FoundationOne® CDx
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    Retevmo (selpercatinib)
    20d
    A Study of Participant Reported Preference for Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Over Intravenous Pembrolizumab (MK-3475) Formulation in Multiple Tumor Types (MK-3475A-F11) (clinicaltrials.gov)
    P2, N=144, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Keytruda (pembrolizumab)
    21d
    Targeting CNS Metastases in Non-Small Cell Lung Cancer With Evolving Approaches Using Molecular Markers: A Review. (PubMed, JAMA Oncol)
    With multiple generations of targeted therapies now available, the treatment for CNS metastases should be tailored to the patients with consideration given to molecular testing results, CNS penetrance of systemic therapy, patient characteristics, and multidisciplinary review. More research is needed in understanding the clonal evolution of CNS metastases, and the development of novel therapeutics with CNS efficacy.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    21d
    ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
    P1, N=279, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • ALK-ROS1 fusion • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
    |
    paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
    22d
    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
    |
    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)
    |
    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
    |
    BNT324
    23d
    A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P3, N=121, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2035 --> Sep 2033 | Trial primary completion date: Jun 2029 --> Aug 2032
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    RET fusion • ALK fusion • ROS1 fusion
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • Rozlytrek (entrectinib) • Alecensa (alectinib)
    23d
    Determining Line of Therapy from Real-World Data in Non-Small Cell Lung Cancer. (PubMed, Pharmacoepidemiol Drug Saf)
    These rules provide an updated framework to evaluate current treatment patterns, accounting for the increased use of targeted therapies in patients with mNSCLC, and promote standardization of methods for determining LOT from real-world data.
    Journal • Real-world evidence • Real-world
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation
    23d
    Evaluation of the efficacy of PD‑1/PD‑L1 inhibitor plus bevacizumab and chemotherapy for the treatment of patients with driver gene‑negative advanced‑stage lung adenocarcinoma: A retrospective cohort study. (PubMed, Oncol Lett)
    Moreover, the incidence of each adverse event did not differ significantly between the PBC and BC groups. In conclusion, the present study demonstrated that the PBC regimen serves as a superior treatment option for patients with driver gene-negative advanced-stage lung adenocarcinoma; however, further verification of its efficacy is still required.
    Retrospective data • Journal • PD(L)-1 Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PD-1 (Programmed cell death 1)
    |
    Avastin (bevacizumab)
    23d
    Biological and clinical characteristics of non-small cell lung cancer non-specific subtype. (PubMed, Heliyon)
    Among 69 patients with complete treatment information, 58 received platinum-based chemotherapy, with paclitaxel being the most commonly used combination chemotherapy drug (n = 25), followed by pemetrexed (n = 21). Paclitaxel with immunotherapy may have better benefits as a first-line treatment. Anatomic location and immunotherapy use are prognostic factors.
    Journal • IO biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NKX2-1 (NK2 Homeobox 1) • NAPSA (Napsin A Aspartic Peptidase)
    |
    KRAS mutation • EGFR mutation
    |
    paclitaxel • pemetrexed
    23d
    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
    |
    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)
    |
    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
    23d
    Entrectinib-Induced Myocarditis and Acute Heart Failure Responding to Steroid Treatment: A Case Report. (PubMed, JTO Clin Res Rep)
    His treatment was subsequently changed to crizotinib, which was well tolerated. This case was also associated with concurrent acute heart failure after entrectinib treatment which responded promptly to prednisolone (40 mg). Entrectinib-induced cardiotoxicity is an important adverse event to be aware of, particularly as patients may be asymptomatic for an initial period before significant deterioration.
    Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ROS1 positive
    |
    Xalkori (crizotinib) • Rozlytrek (entrectinib)
    24d
    Brief Report: Final overall survival and long-term safety of lorlatinib in patients with ALK-positive non-small cell lung cancer from the pivotal phase 2 study. (PubMed, J Thorac Oncol)
    After a minimum follow-up of 5 years, final analyses from the global phase 2 study confirmed substantial activity, prolonged OS, and generally consistent safety findings with lorlatinib in treatment-naïve and previously treated patients with ALK-positive NSCLC.
    P2 data • Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • ALK mutation
    |
    Xalkori (crizotinib) • Lorbrena (lorlatinib)
    25d
    Phase II trial of consolidative stereotactic body radiation therapy in patients with metastatic oncogene-driven non-small cell lung carcinoma treated with tyrosine kinase inhibitors. (PubMed, Int J Radiat Oncol Biol Phys)
    In patients treated with first-line TKIs, consolidative SBRT was associated with improvement in distant disease control compared with historical controls, supporting ongoing randomized trials.
    P2 data • Journal • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation
    27d
    Real-World Study on Implementation of Genomic Tests for Advanced Lung Adenocarcinoma in Brazil. (PubMed, JCO Glob Oncol)
    This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
    |
    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 • PD-L1 overexpression • KRAS G12C • BRAF V600 • EGFR exon 20 insertion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • KRAS G12 • EGFR exon 20 mutation • ALK-ROS1 fusion • KRAS G12C + PD-L1 expression
    27d
    Inhibition of ROS1 activity with lorlatinib reversibly suppresses fertility in male mice. (PubMed, Andrology)
    Inhibition of ROS1 with lorlatinib suppressed sperm maturation and male fertility reversibly. Future exploration of molecules that specifically target ROS1 and the ROS1 pathway in the epididymis may lead to the development of safe and reversible male contraceptives.
    Preclinical • Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RNASE1 (Ribonuclease A Family Member 1)
    |
    Lorbrena (lorlatinib)
    28d
    Lorlatinib-associated weight gain and dyslipidaemia: A retrospective analysis and implications for future care. (PubMed, Lung Cancer)
    Weight gain and dyslipidaemia are commonly observed with lorlatinib, highlighting the need for effective pharmacologic and non-pharmacologic strategies to manage these toxicities. Rates were similar to those reported in the CROWN trial. Given the 60 % 5-year progression-free survival (PFS) demonstrated in CROWN, mitigation of treatment-related toxicities is paramount to minimise impact on patient quality of life (QOL) and cancer-independent morbidity in this subgroup of NSCLC patients with favourable outcomes.
    Retrospective data • Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • ROS1 positive • ALK positive + ROS1 positive
    |
    Lorbrena (lorlatinib)
    29d
    Prognostic significance of actionable next-generation sequencing multigene panel in esophageal cancer treatment. (PubMed, Eur Rev Med Pharmacol Sci)
    The utility of an actionable multigene panel revealed the value of a well-designed NGS workflow in the practical use of clinical outcomes via the prediction of responsiveness to therapeutic agents or indications for novel treatment modalities in addition to the estimation of prognosis.
    Journal • Next-generation sequencing
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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) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    PTEN mutation
    29d
    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)
    30d
    BRIO: Propranolol Hydrochloride in Combination With Sintilimab and Platinum-based Chemotherapy for Treatment of Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=6, Recruiting, Second Xiangya Hospital of Central South University | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    ALK fusion • ROS1 fusion
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    cisplatin • carboplatin • Tyvyt (sintilimab) • albumin-bound paclitaxel
    1m
    Investigating the safety of photobiomodulation in oral carcinogenesis: insights into cell proliferation, invasion, and apoptosis via the 4NQO model. (PubMed, Sci Rep)
    No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins.
    Journal
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    1m
    Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison. (PubMed, Lung Cancer)
    The outcomes in this MAIC study including Asian patients with ROS1-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.
    Journal
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    ROS1 positive
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    Xalkori (crizotinib) • Rozlytrek (entrectinib)
    1m
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
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    FoundationOne® CDx
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)