背景:原肌球蛋白受体激酶(TRKs)对许多细胞功能至关重要,比如增长,运动性,分化,和新陈代谢。异常的TRK信号导致多种人类疾病,最明显的癌症。全面的基因组研究已经发现了编码像MET这样的TRK的基因的许多变化,HER2/ErbB2和EGFR,在许多其他人中。精准医学耐药,由于蛋白质点突变而发生复发,并且多个分子反馈回路的存在是TRK抑制剂作为癌症治疗的一般治疗剂的长期有效性的重要障碍。
目的:本综述旨在强调原肌球蛋白受体激酶在癌症中的作用以及TRK抑制剂在癌症干预中的作用。
方法:文献研究是使用GoogleScholar和ScienceDirect等数据库完成的,WOS,PubMed,SciFinder,还有Scopus.
结果:在这篇综述中,我们概述了TRKs及其抑制剂的主要分子和功能特性。它还讨论了这些进展如何影响由激活的TRK引起的恶性肿瘤和其他疾病的新型治疗方法的发展和使用。几种治疗策略,包括发现和开发属于各种化学类别的小分子TRK抑制剂及其活性,以及对受体的选择性,已经详细讨论过了。
结论:这篇综述将帮助研究人员获得对TRK的基本理解,这个蛋白质家族是如何工作的,以及产生化学部分的方法,如TRK抑制剂,可以作为癌症的定制疗法。
BACKGROUND: The tropomyosin receptor kinases (TRKs) are crucial for many cellular functions, such as growth, motility, differentiation, and metabolism. Abnormal TRK signalling contributes to a variety of human disorders, most evidently cancer. Comprehensive genomic studies have found numerous changes in the genes that code for TRKs like MET, HER2/ErbB2, and EGFR, among many others. Precision medicine resistance, relapse occurring because of the protein point mutations, and the existence of multiple molecular feedback loops are significant therapeutic hurdles to the long-term effectiveness of TRK inhibitors as general therapeutic agents for the treatment of cancer.
OBJECTIVE: This
review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer.
METHODS: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus.
RESULTS: In this
review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail.
CONCLUSIONS: This
review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer.