ROS1

Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ROS1 gene.

Function

This proto-oncogene, highly expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor.

Interactions

ROS1 (gene) has been shown to interact with PTPN6.

Role in cancer

Gene rearrangements involving the ROS1 gene were first detected in glioblastoma tumors and cell lines. In 2007 a ROS1 rearrangement was identified in a cell line derived from a lung adenocarcinoma patient. Since that discovery, multiple studies have demonstrated an incidence of approximately 1% in lung cancers, demonstrated oncogenicity, and showed that inhibition of tumor cells bearing ROS1 gene fusions by crizotinib or other ROS1 tyrosine kinase inhibitors was effective in vitro. Clinical data supports the use of crizotinib in lung cancer patients with ROS1 gene fusions. Preclinical and clinical work suggests multiple potential mechanisms of drug resistance in ROS1+ lung cancer, including kinase domain mutations in ROS1 and bypass signaling via RAS and EGFR. Although the most preclinical and clinical studies of ROS1 gene fusions have been performed in lung cancer, ROS1 fusions have been detected in multiple other tumor histologies, including ovarian carcinoma, sarcoma, cholangiocarcinomas and others. Crizotinib or other ROS1 inhibitors may be effective in other tumor histologies beyond lung cancer as demonstrated by a patient with an inflammatory myofibroblastic tumor harboring a ROS1 fusion with a dramatic response to crizotinib.