Ros1-KO Mouse

ROS1, a proto-oncogene, encodes a receptor tyrosine kinase. Its physiological role in humans remains unclear, but it has been associated with driving cancer development. Somatic chromosomal fusions of ROS1 generate chimeric oncoproteins that can activate downstream signaling pathways, promoting cell proliferation, activation, and cell cycle progression, which accelerates the development of various cancers, especially non-small-cell lung cancer (NSCLC) [1,2].

ROS1-directed tyrosine kinase inhibitors (TKIs) are effective against ROS1-fusion positive cancers. However, resistance can emerge through intrinsic or extrinsic mechanisms. Some factors influencing resistance acquisition include the subcellular localization of ROS1 oncoprotein and TKI properties. Higher-affinity next-generation ROS1 TKIs have been developed to improve intracranial activity and mitigate resistance mechanisms, demonstrating clinical efficacy [1]. ROS1-rearranged NSCLC, which makes up about 1%-2% of all NSCLC, can be detected by various assays. Treatment usually starts with TKIs, but tumors may develop resistance over time through secondary kinase mutations or activation of bypass signaling pathways [3,4].

In conclusion, ROS1 is a key player in cancer biology, especially in NSCLC. Understanding its role in driving cancer and the mechanisms of resistance to TKIs is crucial. The development and study of ROS1-targeted therapies, along with the investigation of resistance mechanisms, contribute to improving the treatment of ROS1-related cancers.