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

Proto-oncogene tyrosine-protein kinase ROS (ROS1) is a receptor tyrosine kinase belonging to the insulin receptor family that plays a significant role in cell growth, survival, and differentiation [2, 4, 14]. While its exact physiological role in humans is not fully characterized, it is known to be involved in the development of the epididymal epithelium [2, 14]. ROS1 is a well-established oncogenic driver in several malignancies, most notably non-small cell lung cancer (NSCLC), where chromosomal rearrangements result in the expression of constitutively active ROS1 fusion proteins [1, 6, 18]. These fusions, such as CD74-ROS1, trigger downstream signaling pathways like MAPK/ERK and PI3K/AKT, leading to uncontrolled cellular proliferation [1, 2, 5]. Crizotinib, originally developed as an ALK and MET inhibitor, was the first targeted therapy approved for ROS1-rearranged cancers due to the structural similarity between the ALK and ROS1 kinase domains [6, 8, 9]. Despite high initial response rates, patients often develop resistance through secondary mutations in the ROS1 kinase domain, such as the G2032R solvent front mutation, necessitating the use of next-generation inhibitors like entrectinib and repotrectinib [13, 15, 16, 18].

Other names

ROS proto-oncogene 1, receptor tyrosine kinaseMCF3ROSc-ros-1Proto-oncogene c-rosV-ros avian UR2 sarcoma virus oncogene homolog 1

Tyrosine kinase inhibition