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.

中文翻译：

---

表皮生长因子受体：选择性细胞内递送的关键

表皮生长因子受体 (EGFR) 是一种整合的表面蛋白，介导细胞对多种生长因子的反应。由于突变，其过度表达和激活增加是许多类型癌症最常见的特征之一。阻断 EGFR 激活的药物的开发和临床应用成为个性化靶向药物的一个主要例子。然而，尽管在该领域取得了明显的成功，但在大多数情况下，癌症治愈仍然遥不可及。正因为如此，以及寻找克服治疗困难的​​可能方法的结果，大量新的治疗方法依赖于使用EGFR过表达及其变化来破坏癌细胞。关于 EGFR、其天然配体的结构、功能和细胞内转运的现代数据，本综述总结和分析了 EGFR 激活引发的信号级联反应、EGFR 表达和激活在肿瘤疾病中的特点，以及旨在阻断 EGFR 信号通路的应用治疗方法。详细回顾了靶向递送各种化学治疗剂、放射性核素、免疫毒素、光敏剂的方法，以及针对 EGFR 过度表达的癌细胞的基因治疗的前景。应该指出的是，如今人们越来越关注多功能系统的开发，这些系统要么携带多种不同的活性剂，要么拥有多种环境相关的运输功能。