Oncogenic fusions: Targeting NTRK
Garo Hagopian, Misako Nagasaka
Abstract
Non-Small Cell Lung Cancer (NSCLC) is responsible for the highest number of cancer-related deaths in the United States. Thankfully, advancements in the detection and targeting of gene mutations have greatly improved outcomes for many patients. One significant mutation driving oncogenesis in various cancers, including NSCLC, is the neurotrophic tyrosine receptor kinase (NTRK ) fusion. Presently, larotrectinib and entrectinib are the only FDA-approved therapies for NTRK -mutated cancers. Despite the efficacy and tolerability exhibited by these therapies, several clinical hurdles persist for physicians, including resistance mutations and limited penetration of the central nervous system (CNS), which diminishes their effectiveness. The treatment landscape for NTRK cancers is still being explored, with numerous new tyrosine kinase inhibitors currently in development or undergoing phase 1 and 2 clinical trials. In this review, we delve into both established and novel therapies targeting NTRK -mutated NSCLC. • The presence of neurotrophic tyrosine receptor kinase (NTRK) fusion has been recognized as a causative factor in multiple cancers. • Larotrectinib and enterectinib have obtained approval for the treatment of NTRK-mutated cancers. • In this review, we examined the currently available as well as new NTRK inhibitors in development.