High affinity nerve growth factor receptor (NTRK1) (NTRK1)

High affinity nerve growth factor receptor (NTRK1), also known as TRKA, is a member of the neurotrophic tyrosine kinase receptor family that plays a critical role in the development and maintenance of the nervous system [UniProt, MedlinePlus]. It primarily binds nerve growth factor (NGF), triggering autophosphorylation and activating downstream signaling pathways like MAPK, PI3K, and PLC-gamma to promote neuronal survival and differentiation [UniProt, NIH]. In oncology, NTRK1 is a significant therapeutic target because chromosomal rearrangements can lead to NTRK gene fusions, resulting in constitutively active chimeric proteins that drive various solid tumors [Frontiers in Pharmacology, MDPI]. Drugs like larotrectinib and entrectinib are FDA-approved tumor-agnostic therapies that selectively inhibit these fusion proteins, providing high response rates across multiple cancer types [AACR, NIH]. Beyond cancer, mutations in NTRK1 are linked to congenital insensitivity to pain with anhidrosis (CIPA), highlighting its essential role in sensory perception [MedlinePlus, NIH]. Therapeutic challenges include the development of resistance mutations in the kinase domain, which has led to the development of second-generation inhibitors like selitrectinib [MDPI, AACR].

Other names

TRKTRKATrk-AMTCTRK1p140-TrkAgp140trkNeurotrophic tyrosine kinase receptor type 1Tropomyosin receptor kinase A

Tyrosine kinase inhibition [Frontiers in Pharmacology, NIH]