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  • Title: Discovery of Tropomyosin Receptor Kinase Inhibitors as New Generation Anticancer Agents: A Review.
    Author: Panchal I, Tripathi RKP, Parmar K, Yadav MR.
    Journal: Curr Top Med Chem; 2024; 24(1):3-30. PubMed ID: 38058091.
    Abstract:
    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. CONCLUSION: 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.
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