Research Progress on Small Molecules Inhibitors Targeting TRK Kinases

Background: Trk gene fusions are an important driver in the development of cancers, including secretory breast cancer and infantile congenital sarcoma. Since the first-generation of small molecule Trk inhibitors (Larotrectinib and Entrectinib) came to market, research on small molecule TRK inhibitors, especially second-generation inhibitors that break through the resistance problem, has developed rapidly. Therefore, this article focuses on the research progress of first-generation drugs and second-generation drugs that break through drug resistance. Methods: We used the database to search for relevant and cutting-edge documents, and then filtered and selected them based on the content. The appropriate articles were analyzed and classified, and finally, the article was written according to the topics. Results: The phenomenon of Trk protein fusion and its relation to tumors are described, followed by an explanation of the composition and signaling pathways of Trk kinases. The representative Trk inhibitors and the development of novel Trk inhibitors are classified according to whether they overcome drug resistance problems. Conclusion: This paper provides a theoretical reference for the development of novel inhibitors by introducing and summarizing the representative and novel Trk inhibitors that break through the drug resistance problem.