Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 54 4 2025 04 01 710 722 Jielin Li Department of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, China Yuan Liang Department of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, China 2024 07 04 2024 12 06 NTRK gene is responsible for encoding TRK, which consists of three family members: NTRK1, NTRK2, and NTRK3. These family members encode different proteins known as TRKA, TRKB, and TRKC, respectively. NTRK fusion genes are the clearest driving factor for carcinogenesis. NTRK gene fusion detection and TRK inhibitors are effective measures for the treatment of malignant tumors. The development of anti-tumor drugs targeting TRK proteins has been favored by various scientific research institutions and pharmaceutical companies. The first-generation TRK inhibitors, larotrectinib and entrectinib, have been approved for the treatment of pediatric and adult patients with metastatic or locally advanced solid tumors harboring NTRK fusion proteins, demonstrating remarkable anticancer efficacy in clinical settings. However, the issue of acquired resistance to TRK inhibitors has emerged. Currently, efforts are underway to develop next-generation TRK inhibitors based on sequence, structural, and kinetic methodologies, as well as to explore the intracellular signaling pathways of TRK and the mechanisms underlying resistance. The main focus of this review was to discuss the fusion of NTRK genes and the application of TRK inhibitor treatment. https://ijph.tums.ac.ir/index.php/ijph/article/view/35967 https://ijph.tums.ac.ir/index.php/ijph/article/download/35967/8513