Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (NTRK1, NTRK2 and NTRK3) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLCγ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.

原肌球蛋白受体激酶 A、B 和 C（TRKA、TRKB 和 TRKC）是细胞表面受体酪氨酸激酶 (RTK) 家族的知名成员，由神经营养受体酪氨酸激酶 1、2 和 3 ( NTRK1, NTRK2和NTRK3 ) 基因，分别。TRKs可以通过RAS/MAPKs、PI3K/AKT和PLCγ途径调节细胞增殖、分化甚至凋亡。涉及NTRK的基因融合作为多种成人和儿童肿瘤的致癌驱动因子，TRK 已成为有希望的抗肿瘤靶点。因此，迫切需要全面了解 TRK 和相关的 TRK 抑制剂，以进一步开发具有潜在临床应用价值的新型 TRK 抑制剂。本综述重点总结了 TRK 和NTRK融合蛋白的生物学功能、具有不同化学型的小分子 TRK 抑制剂的开发及其活性和选择性，以及这些抑制剂在未来癌症药物发现工作中的潜在治疗应用。