Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, Zhejiang, China.
State Key Laboratory of Biotherapy & Cancer Center, West China Hospital, Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, 610041, China.
Future Med Chem. 2024;16(18):1923-1944. doi: 10.1080/17568919.2024.2389764. Epub 2024 Aug 29.
Abnormal activation of EGFR is often associated with various malignant tumors, making it an important target for antitumor therapy. However, traditional targeted inhibitors have several limitations, such as drug resistance and side effects. Many studies have focused on the development of EGFR degraders to overcome this resistance and enhance the therapeutic effect on tumors. Proteolysis targeting chimeras (PROTAC) and Lysosome-based degradation techniques have made significant progress in degrading EGFR. This review provides a summary of the structural and function of EGFR, the resistance, particularly the research progress and activity of EGFR degraders via the proteasome and lysosome. Furthermore, this review aims to provide insights for the development of the novel EGFR degraders.
表皮生长因子受体（EGFR）的异常激活常与各种恶性肿瘤相关，使其成为抗肿瘤治疗的重要靶点。然而，传统的靶向抑制剂存在耐药性和副作用等多种局限性。许多研究集中于开发 EGFR 降解剂以克服这种耐药性并增强对肿瘤的治疗效果。蛋白水解靶向嵌合体（PROTAC）和基于溶酶体的降解技术在 EGFR 降解方面取得了重大进展。本综述总结了 EGFR 的结构和功能、耐药性，特别是通过蛋白酶体和溶酶体降解 EGFR 的降解剂的研究进展和活性。此外，本综述旨在为新型 EGFR 降解剂的开发提供思路。
