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

Anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) are evolutionarily related receptor tyrosine kinases belonging to the insulin receptor superfamily. Both are integral membrane proteins with extracellular ligand-binding domains, a single transmembrane domain, and cytoplasmic regions featuring tyrosine kinase activity. In healthy tissue, ALK expression is largely confined to the nervous system, whereas the physiological role of ROS1 is less defined but involves epithelial cell differentiation. Both ALK and ROS1 can undergo chromosomal rearrangements that fuse their kinase domains to various partners, resulting in constitutively activated kinases, which drive tumor growth through persistent oncogenic signaling. Such fusions are observed in 3-5% (ALK) and ~1-2% (ROS1) of NSCLC cases, predominantly in younger, non-smoking patients with adenocarcinoma histology. Detection of these rearrangements is clinically critical, as tumors harboring ALK or ROS1 fusions are highly sensitive to specific tyrosine kinase inhibitors like crizotinib, which block their signaling and can induce dramatic clinical responses in affected patients. Nevertheless, resistance to these drugs frequently emerges, prompting the development of newer, more potent and selective inhibitors as well as combination approaches. Routine molecular diagnostics for ALK and ROS1 rearrangements now guide targeted therapy choices for lung and other cancers.

Other names

Anaplastic lymphoma kinaseALK receptorALK tyrosine kinaseProto-oncogene tyrosine-protein kinase ROSc-ros oncogene 1ROS

Inhibition of tyrosine kinase activity, leading to blockade of receptor-mediated oncogenic signaling pathways. Induction of cell cycle arrest and apoptosis in fusion-positive cancer cells.