Tropomyosin receptor kinase A, B, and C and ROS proto-oncogene 1 receptor tyrosine kinase (TRKA, TRKB, TRKC, and ROS1)

Tropomyosin receptor kinases A, B, and C (encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively) are membrane-bound receptor tyrosine kinases critically involved in neural development, differentiation, and cell survival[1][2][3]. They bind specific neurotrophin ligands (NGF for TRKA, BDNF and NT-4/5 for TRKB, NT-3 for TRKC), initiating downstream MAPK, PI3K, and PLCγ signaling cascades. Chromosomal rearrangements or gene fusions involving NTRK1/2/3 or ROS1 lead to constitutive kinase activation, promoting oncogenic signaling and driving tumor growth in multiple cancer types[4][5]. These fusions occur in a small percentage of all solid tumors but are highly actionable, with targeted inhibitors (e.g., larotrectinib, entrectinib) showing significant clinical efficacy. ROS1 (ROS proto-oncogene 1 receptor tyrosine kinase) is a separate, structurally similar tyrosine kinase also implicated in cancer through gene fusions, primarily in non–small cell lung cancer and other rare tumors. The name "NTRK1/2/3 and ROS1" combines several distinct, but clinically related, actionable kinase fusion targets used in oncology[4][5].

Other names

TRKATRKBTRKCc-ROS receptor tyrosine kinaseROS proto-oncogene 1

Small molecule inhibitors block the tyrosine kinase activity, inhibiting downstream oncogenic signaling pathways in tumors harboring activating fusions or mutations[2][3]. Induce apoptosis and reduce proliferation by blocking neurotrophin or aberrant ligand-independent activation.