Anaplastic lymphoma kinase and Proto-oncogene tyrosine-protein kinase ROS1 (ALK and ROS1)

Anaplastic lymphoma kinase (ALK) and ROS1 are receptor tyrosine kinases of the insulin receptor superfamily that act as oncogenic drivers in various cancers through gene fusions, rearrangements, or activating mutations[1][3][4][5]. Both proteins possess extracellular ligand-binding domains, a transmembrane region, and intracellular kinase domains, which drive aberrant cell signaling when constitutively activated by fusion events[5][7]. ALK fusions (such as NPM-ALK) and ROS1 fusions (such as CD74-ROS1) are frequent actionable mutations in non-small cell lung cancer, and their presence defines a distinct subset of patients—often younger, non-smokers, and adenocarcinoma histology—who are highly responsive to targeted kinase inhibitors like crizotinib, cabozantinib, and newer agents[2][3][1]. Resistance to inhibitors arises through mutation of the kinase domain, prompting ongoing research for next-generation therapeutics[2][3]. Both ALK and ROS1 are validated therapeutic targets, and molecular testing for their gene rearrangements is standard in the clinical management of advanced lung cancer[1][3].

Other names

ALK tyrosine kinase receptorCD246 (cluster of differentiation 246)NPM-ALK (fusion protein)ROSROS1 kinaseCD74-ROS1FIG-ROS1SLC34A2-ROS1EZR-ROS1TPM3-ROS1SDC4-ROS1

Inhibition of tyrosine kinase activity, blocking downstream oncogenic signaling and cell proliferation Competitive inhibition at the ATP binding site of the kinase domain