Liu Ju, Zhang Yadong, Zhu Yan, Tian Lu, Tang Mingrui, Shen Jiwei, Chen Ye, Ding Shi
College of Pharmacy of Liaoning University, Shenyang, Liaoning 110036, P. R. China.
API Engineering Tech-nology Research Center of Liaoning Province, Shenyang, Liaoning 110036, P. R. China.
Curr Med Chem. 2023;30(10):1175-1192. doi: 10.2174/0929867329666220801145639.
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.
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.
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.
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.
Trk基因融合是包括分泌性乳腺癌和婴儿先天性肉瘤在内的癌症发展的重要驱动因素。自第一代小分子Trk抑制剂（拉罗替尼和恩曲替尼）上市以来，小分子TRK抑制剂的研究，尤其是突破耐药性问题的第二代抑制剂的研究发展迅速。因此，本文重点关注第一代药物和突破耐药性的第二代药物的研究进展。
我们利用数据库搜索相关前沿文献，然后根据内容进行筛选和选择。对合适的文章进行分析和分类，最后根据主题撰写本文。
描述了Trk蛋白融合现象及其与肿瘤的关系，随后解释了Trk激酶的组成和信号通路。代表性的Trk抑制剂和新型Trk抑制剂根据是否克服耐药性问题进行分类。
本文通过介绍和总结突破耐药性问题的代表性和新型Trk抑制剂，为新型抑制剂的开发提供了理论参考。
