ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)

ROS proto-oncogene 1 (ROS1) encodes a type I integral membrane protein that functions as a receptor tyrosine kinase. It is structurally related to anaplastic lymphoma kinase (ALK) and belongs to the insulin receptor family. While its physiological ligand and normal biological role remain unclear in humans, somatic chromosomal fusions involving *ROS1* produce constitutively active chimeric oncoproteins that drive oncogenesis across several cancers. These fusions are most notably found in about 1% of non-small cell lung cancers but also occur in other malignancies such as glioblastoma and cholangiocarcinoma. Tumors harboring *ROS1* fusions are highly sensitive to specific small molecule inhibitors like crizotinib. However, resistance can develop through secondary mutations or bypass signaling mechanisms. The detection of *ROS1* rearrangements serves both as a biomarker for patient selection and as an actionable therapeutic target in precision oncology[4][5][6][8][9].

Other names

c-ros-1MCF3ROSProto-oncogene tyrosine-protein kinase ROS[5][6]

Inhibition of constitutively active fusion kinases resulting from chromosomal rearrangements involving the ROS1 gene; these drugs block downstream signaling pathways such as RAS–MEK–ERK, JAK–STAT3, PI3K–AKT–mTOR[9].