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|Gene Variant Descriptions||ROS1 L1951R lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1951R has been demonstrated to confer resistance to Ros1 tyrosine kinase inhibitors in the context of a Ros1 fusion in culture (PMID: 25351743), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2022).|
|Associated Drug Resistance||Y|
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ROS1 fusion ROS1 L1951R ROS1 L2026M||lung non-small cell carcinoma||resistant||Ceritinib||Case Reports/Case Series||Actionable||In a clinical study, a non-small cell lung carcinoma patient co-harboring a ROS1 fusion, and two other mutations in trans, ROS1 L2026M, and ROS1 L1951R demonstrated resistance to treatment with Zykadia (ceritinib), and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358).||29636358|
|ROS1 fusion ROS1 L1951R ROS1 L2026M||lung non-small cell carcinoma||predicted - resistant||Crizotinib||Case Reports/Case Series||Actionable||In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion progressed after 17 months of treatment with Xalkori (crizotinib), and was found to have acquired two additional mutations in trans, ROS1 L2026M and ROS1 L1951R, and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358).||29636358|