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    BIOMARKER:

    ROS1 S1986Y

    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:
    6098
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Associations

    News

    Trials
    8ms
    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)
    |
    ROS1 rearrangement • ROS1 G2032R • ROS1 S1986Y
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    Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Augtyro (repotrectinib)
    over1year
    Dissecting the molecular landscape of resistance to ROS1 tyrosine kinase inhibitors with improved NSCLC pre-clinical models. (ELCC 2023)
    Results G2032R line showed in 2D the strongest resistance towards crizotinib, entrectinib and ceritinib, having all a weak activity (IC50 s around 1,1 μM), opposed to repotrectinib (93,25 nM) and lorlatinib (317,17 nM). These results were confirmed by western blot. Our approach allows the generation of patient-derived mutant cell lines and screened for TKI sensitivity guided by the in silico modelling of ROS1 variants.
    Preclinical
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ROS1 G2032R • ROS1 S1986Y
    |
    Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Augtyro (repotrectinib)