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Ref Type Journal Article
PMID (23719267)
Authors Davies KD, Doebele RC
Title Molecular pathways: ROS1 fusion proteins in cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 19
Issue 15
Date 2013 Aug 01
URL
Abstract Text Genetic alterations that lead to constitutive activation of kinases are frequently observed in cancer. In many cases, the growth and survival of tumor cells rely upon an activated kinase such that inhibition of its activity is an effective anticancer therapy. ROS1 is a receptor tyrosine kinase that has recently been shown to undergo genetic rearrangements in a variety of human cancers, including glioblastoma, non-small cell lung cancer (NSCLC), cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, and epithelioid hemangioendothelioma. These rearrangements create fusion proteins in which the kinase domain of ROS1 becomes constitutively active and drives cellular proliferation. Targeting ROS1 fusion proteins with the small-molecule inhibitor crizotinib is showing promise as an effective therapy in patients with NSCLC whose tumors are positive for these genetic abnormalities. This review discusses the recent preclinical and clinical findings on ROS1 gene fusions in cancer.

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Gene Name Source Synonyms Protein Domains Gene Description Gene Role
ROS1 NCBI MCF3|ROS|c-ros-1 ROS1, ROS proto-oncogene 1, receptor tyrosine kinase, is an orphan receptor tyrosine kinase that may activates multiple pathways involved in cell survival and transformation (PMID: 23719267, PMID: 32327173). ROS1 fusion proteins frequently lead to constitutive activation of Ros1 signaling and have been identified in glioblastoma, non-small cell lung cancer, cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, glioma, and epithelioid hemangioendothelioma (PMID: 23719267, PMID: 30262706, PMID: 30171048, PMID: 3004937), and ROS1 mutations are often associated with acquired resistance to inhibition (PMID: 31256210). Oncogene
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References