Proto-oncogene tyrosine-protein kinase ROS receptor (ROS1)

Proto-oncogene tyrosine-protein kinase ROS receptor (commonly abbreviated as **ROS1**) is a type I integral membrane protein with intrinsic **receptor tyrosine kinase** activity. It belongs to the insulin receptor family and plays a role in downstream signaling processes that regulate cell growth and differentiation. The *ROS1* gene is highly expressed in various tumor cell lines and has been identified as an oncogenic driver through chromosomal rearrangements that create constitutively active fusion proteins. These fusions are particularly relevant in non-small cell lung cancer but have also been observed in other malignancies such as glioblastoma, cholangiosarcoma, ovarian cancer, angiosarcoma, gastric cancer, colorectal cancer, and spitzoid melanoma. Therapeutically targeting aberrant *ROS1* activity—most notably using small-molecule inhibitors like crizotinib—has shown significant clinical benefit for patients whose tumors harbor activating *ROS1* fusions. Detection of these fusions serves both as a biomarker for patient selection and efficacy monitoring. However, resistance mechanisms can emerge during treatment. The normal physiological ligand(s) for this "orphan" RTK remain unclear; its primary significance lies in its pathological activation via gene fusion events rather than normal biological function.

Other names

ROS1c-rosROS proto-oncogene 1, receptor tyrosine kinaseProto-oncogene tyrosine-protein kinase ROS

Inhibition of the tyrosine kinase activity of the fusion protein or mutant receptor to block downstream oncogenic signaling pathways