Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.
Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.
No abstract
In 2022, 2.3 million new cases of breast cancer were registered in the world, which accounted for 11.6% of the total number of malignant neoplasms. Depending on the tumor's molecular profile, the prognosis for patients can be different. One of the most aggressive types is HER2-positive breast cancer. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, is used to treat such tumors. Congenital or acquired resistance to trastuzumab is one of the essential problems in clinical oncology. Our study aimed to investigate the resistance mechanisms to trastuzumab and ways to overcome them. This drug influences several directions of oncogenesis at the same time. The fundamental mechanisms of action of trastuzumab are inhibition of HER2 ectodomain shedding, inhibition of angiogenesis, degradation of HER2 protein and its internalization, inhibition of DNA repair, influence on the phosphatidylinositol 3-kinase pathway, cell cycle and antibody-dependent cellular cytotoxicity. The biological mechanisms of resistance to trastuzumab are based on vascular mimicry and hypoxia, the appearance of breast cancer stem cells, activation of alternative signaling pathways, metabolic changes, alternative molecular variants of HER2, changes in the processes of immune regulation, heterogeneity of expression and stability of the HER2 protein. In modern clinical oncology, trastuzumab is used as an original product and as antibody-drug conjugates. Trastuzumab emtansine and trastuzumab deruxtecan are approved for the treatment of patients with HER2-positive breast cancer, including those with low HER2 expression. This literature review identified the biological resistance mechanisms to trastuzumab and ways to overcome them. The implementation of new targeted drugs in combination with trastuzumab is the way to personalized treatment. It can significantly improve the survival of patients with HER2-positive breast cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.