Tropomyosin Receptor Kinase Inhibitors For Locally Advanced Or Metastatic Solid Tumors Harboring An Ntrk Gene Fusion

The tropomyosin receptor kinase (TRK)-receptor family is encoded by the 3 neurotrophic receptor tyrosine kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) that code for 3 proteins. In healthy tissue, the TRK pathway is involved in the development and functioning of the nervous system as well as cell survival. However, NTRK gene fusions, which are rare kinase fusion events, create oncogenic proteins which activate a signaling cascade implicated in cell proliferation, survival, and angiogenesis. Both larotrectinib and entrectinib disrupt the activity of tropomyosin receptor kinase TRK proteins. However, entrectinib additionally inhibits 2 other kinases; anaplastic lymphoma kinase and proto-oncogene tyrosine-protein kinase.