Neurotrophic tropomyosin receptor kinase fusion protein (NTRK fusion protein)

Neurotrophic tropomyosin receptor kinase fusion proteins are chimeric oncoproteins generated by chromosomal rearrangements that fuse the 3’ region of an NTRK gene (NTRK1, NTRK2, or NTRK3) to the 5’ region of another gene. The resulting fusion protein retains the tyrosine kinase domain of TRK proteins, leading to constitutive, ligand-independent activation of downstream signaling pathways involved in cell proliferation and survival (e.g., MAPK, PI3K). These oncogenic fusions are rare overall but are highly prevalent in certain rare pediatric and adult tumors, and are targetable by selective TRK inhibitors such as larotrectinib and entrectinib, which have demonstrated efficacy in NTRK fusion-positive cancers across multiple histologies. Detection of NTRK fusions is now a standard biomarker-driven approach for tumor-agnostic therapy in oncology.

Other names

TRK fusion proteinNeurotrophic tyrosine receptor kinase fusion proteinNTRK1/2/3 fusion proteinTRKA/TRKB/TRKC fusion protein

Inhibition of TRK kinase activity by binding the ATP site of the kinase domain in the fusion protein, preventing downstream signaling (MAPK, PI3K/AKT, PKC, STAT3 pathways), resulting in tumor regression and growth inhibition