REVIEW: Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

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A. A. Rosenkranz^1,2,a* and T. A. Slastnikova²

¹Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

²Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia

^* To whom correspondence should be addressed.

Received June 15, 2020; Revised July 23, 2020; Accepted July 23, 2020

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Epidermal growth factor receptor (EGFR) is an integral surface protein mediating cellular response to a number of growth factors. Its overexpression and increased activation due to mutations is one of the most common traits of many types of cancer. Development and clinical use of the agents, which block EGFR activation, became a prime example of the personalized targeted medicine. However, despite the obvious success in this area, cancer cure remains unattainable in most cases. Because of that, as well as the result of the search for possible ways to overcome the difficulties of treatment, a huge number of new treatment methods relying on the use of EGFR overexpression and its changes to destroy cancer cells. Modern data on the structure, functioning, and intracellular transport of EGFR, its natural ligands, as well as signaling cascades triggered by the EGFR activation, peculiarities of the EGFR expression and activation in oncological disorders, as well as applied therapeutic approaches aimed at blocking EGFR signaling pathway are summarized and analyzed in this review. Approaches to the targeted delivery of various chemotherapeutic agents, radionuclides, immunotoxins, photosensitizers, as well as the prospects for gene therapy aimed at cancer cells with EGFR overexpression are reviewed in detail. It should be noted that increasing attention is being paid nowadays to the development of multifunctional systems, either carrying several different active agents, or possessing several environment-dependent transport functions. Potentials of the systems based on receptor-mediated endocytosis of EGFR and their possible advantages and limitations are discussed.

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KEY WORDS: epidermal growth factor receptor, overexpression, endocytosis, cancer, targeted cancer therapy, drug delivery

DOI: 10.1134/S0006297920090011

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