Discovery of Tropomyosin Receptor Kinase Inhibitors as New Generation Anticancer Agents: A Review

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 stud-ies 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 pro-tein point mutations, and the existence of multiple molecular feedback loops are significant thera-peutic 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 can-cer 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 devel-opment 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 to-wards 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.