Singh Satyam, Sadhukhan Sushabhan, Sonawane Avinash
Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Madhya Pradesh 453 552, India.
Department of Chemistry, Indian Institute of Technology Palakkad, Kerala 678 623, India; Department of Biological Sciences & Engineering, Indian Institute of Technology Palakkad, Kerala 678 623, India.
Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188967. doi: 10.1016/j.bbcan.2023.188967. Epub 2023 Aug 30.
Epidermal growth factor receptor (EGFR) actively involves in modulation of various cancer progression related mechanisms including angiogenesis, differentiation and migration. Therefore, targeting EGFR has surfaced as a prominent approach for the treatment of several types of cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer, glioblastoma. Various first, second and third generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated effectiveness as an anti-cancer therapeutics. However, rapid development of drug resistance and mutations still remains a major challenge for the EGFR-TKIs therapy. Overcoming from intrinsic and acquired resistance caused by EGFR mutations warrants the further exploration of alternative strategies and discovery of novel inhibitors. In this review, we delve into the breakthrough discoveries have been made in previous 20 years, and discuss the currently ongoing efforts aimed to circumvent the chemo-resistance. We also highlight the new challenges, limitations and future directions for the development of improved therapeutic approaches such as fourth-generation EGFR-TKIs, peptides, nanobodies, PROTACs etc.
表皮生长因子受体（EGFR）积极参与多种与癌症进展相关机制的调节，包括血管生成、分化和迁移。因此，靶向EGFR已成为治疗多种癌症的重要方法，包括非小细胞肺癌（NSCLC）、胰腺癌、胶质母细胞瘤。各种第一代、第二代和第三代EGFR酪氨酸激酶抑制剂（EGFR-TKIs）已证明作为抗癌治疗药物是有效的。然而，耐药性的快速发展和突变仍然是EGFR-TKIs治疗的主要挑战。克服由EGFR突变引起的内在和获得性耐药需要进一步探索替代策略并发现新型抑制剂。在这篇综述中，我们深入探讨了过去20年中取得的突破性发现，并讨论了目前旨在规避化疗耐药性的努力。我们还强调了开发改进治疗方法（如第四代EGFR-TKIs、肽、纳米抗体、PROTAC等）的新挑战、局限性和未来方向。
