Epidermal growth factor receptor blockers – known possibilities and new perspectives in oncology

The epidermal growth factor receptor (EGFR) is a critical signaling molecule that, upon activation, promotes neoplastic transformation and metastasis. The utilization of targeted drugs, specifically EGFR inhibitors, has emerged as a pivotal component in the management of diverse malignant neoplasms. Among them, low-molecular-weight heterocyclic compounds acting as blockers of the EGFR tyrosine kinase domain occupy a key position.

Purpose of the study. Is to conduct analysis of modern literature data devoted to the development and study of the antitumor acttivity of small molecule EGFR inhibitors, with a focus on blockers of the receptor’s intracellular domain.

Materials and methods. A comprehensive literature search was conducted in the PubMed and eLibrary databases. The following keywords were entered into the search engine: "EGFR inhibitors", "small molecular weight kinase inhibitors" (SMKIs), "antitumor effect", "pyrimidine derivatives", "molecular docking", and "molecular modeling". Original research articles, meta-analyses, randomized controlled trials, and systematic reviews published predominantly published within the last five years.

Results. The review presents the main characteristics of small molecule EGFR inhibitors, their mechanisms of action, and classification. The present study explores the underlying causes of resistance to targeted drugs aimed at the internal domain of the receptor, as well as the available strategies for overcoming such drug resistance. The subsequent sections of this text will discuss the development of new EGFR blockers, strategies for increasing their selectivity and efficacy, including through bioinformatic approaches.

Conclusion. Currently, a significant amount of data has been accumulated on the development and use of small molecule heterocyclic EGFR tyrosine kinase inhibitors in the treatment of cancer patients. The main reasons limiting their use in clinical practice are the emergence of resistance due to receptor mutations and toxicity. In this regard, the search for new candidate compounds with a putative antitumor mechanism of action and high affinity to the target remains relevant. Inhibitory activity against the internal domain of EGFR directly depends on the structure of the heterocycle underlying the drug, which must be taken into account when creating new molecules that block this receptor. An important role in this process is played by computer modeling, which allows for a significant reduction in material costs and time. The presented review can be useful for researchers developing domestic targeted drugs aimed at the internal domain of EGFR, as part of import substitution to ensure the technological sovereignty of the Russian Federation.

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