Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
Bioorg Chem. 2020 Jun;99:103811. doi: 10.1016/j.bioorg.2020.103811. Epub 2020 Apr 2.
The identification of molecular agents inhibiting specific functions in cancer cells progression is considered as one of the most successful plans in cancer treatment. The epidermal growth factor receptor (EGFR) over-activation is observed in a vast number of cancers, so, targeting EGFR and its downstream signaling cascades are regarded as a rational and valuable approach in cancer therapy. Several synthetic EGFR tyrosine kinase inhibitors (TKIs) have been evaluated in recent years, mostly exhibited clinical efficacy in relevant models and categorized into first, second, third and fourth-generation. However, studies are still ongoing to find more efficient EGFR inhibitors in light of the resistance to the current inhibitors. In this review, the importance of targeting EGFR signaling pathway in cancer therapy and related epigenetic mutations are highlighted. The recent advances on the discovery and development of different EGFR inhibitors and the use of various therapeutic strategies such as multi-targeting agents and combination therapies have also been reviewed.
鉴定能够抑制癌细胞进展中特定功能的分子制剂被认为是癌症治疗中最成功的方案之一。在大量癌症中观察到表皮生长因子受体（EGFR）过度激活，因此，靶向 EGFR 及其下游信号级联被认为是癌症治疗中的一种合理且有价值的方法。近年来已经评估了几种合成的 EGFR 酪氨酸激酶抑制剂（TKI），它们在相关模型中大多表现出临床疗效，并分为第一代、第二代、第三代和第四代。然而，鉴于对现有抑制剂的耐药性，仍在进行研究以寻找更有效的 EGFR 抑制剂。在这篇综述中，强调了靶向 EGFR 信号通路在癌症治疗中的重要性以及相关的表观遗传突变。还回顾了不同 EGFR 抑制剂的发现和开发的最新进展，以及多靶点药物和联合治疗等各种治疗策略的应用。
