{"type":"root","children":[{"type":"paragraph","children":[{"type":"text","value":"Wildtype ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS-1) is a receptor tyrosine kinase (RTK) containing an N-terminal extracellular domain, a hydrophobic single pass transmembrane region, and a C-terminal intracellular tyrosine kinase domain. It is structurally similar to anaplastic lymphoma kinase (ALK). Exact biological functions of wild type ROS-1 and its ligand are not clearly elucidated. ROS-1 may play a role in various signaling pathways involved in cell growth, proliferation, survival, and differentiation. It is activated by binding to its ligands, leading to receptor dimerization, autophosphorylation, and activation of downstream signaling cascades. ROS-1 gene rearrangement and the expression of ROS-1 fusion proteins have been identified in a number of cancers including glioblastoma, non-small cell lung cancer (NSCLC), cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, and epithelioid hemangioendothelioma. ROS-1 is a validated therapeutic target in non-small cell lung cancer and common ROS-1 fusion partners including, but not limited to CD74, EZR, and SDC4. ROS-1 fusion proteins with constitutively active tyrosine kinase domain can lead to activation of intracellular cell signaling pathways and tumor proliferation."}]}]}