The NeuroTrophin Receptor Kinase (NTRK) family includes three proteins, TRKA, TRKB, and TRKC, encoded by the NTRK1, NTRK2, and NTRK3 genes, these proteins are normally expressed in neural tissues. Activation of TRK structures by NTRK gene fusions is considered as a pan-cancer oncogenic factor.
NTRK gene fusions are found in a variety of adult and pediatric solid tumors. In extremely rare tumor types such as infantile fibrosarcoma and secretory carcinoma, the frequency of NTRK fusion is more than 90%; in common cancers, the fusion frequency is between 0.1% and 2%
NTRK AND TARGETED THERAPY
Although the frequency of NTRK fusions is low in common cancers, the efficacy of NTRK inhibitors is very obvious in patients with NTRK fusion-positive. The FDA approved larotrectinib and entrectinib in 2019 and 2020 for the treatment of patients with advanced solid tumors without alternative therapy or progression , who carry NTRK fusion-positive. This is the second and third pan-cancer FDA-approved tumor-targeted therapy. In clinical trials, the overall response rate (ORR) of larotrectinib and entrectinib reached 75% and 57%, this was achieved after 82% and 63% of the enrolled population had progressed on more than one systemic therapy [2].
Based on the above approval, the National Comprehensive Cancer Network has included NTRK inhibitors in several clinical diagnosis and treatment guidelines. The Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of non-small cell lung cancer (NSCLC) have also included NTRK inhibitors in the first-line treatment of stage IV NTRK fusion-positive NSCLC [3].