Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China.
Tianfu Jincheng Laboratory, Chengdu, 610041, China.
J Hematol Oncol. 2022 Jul 15;15(1):94. doi: 10.1186/s13045-022-01311-6.
Epidermal growth factor receptor (EGFR), the receptor for members of the epidermal growth factor family, regulates cell proliferation and signal transduction; moreover, EGFR is related to the inhibition of tumor cell proliferation, angiogenesis, invasion, metastasis, and apoptosis. Therefore, EGFR has become an important target for the treatment of cancer, including non-small cell lung cancer, head and neck cancer, breast cancer, glioma, cervical cancer, and bladder cancer. First- to third-generation EGFR inhibitors have shown considerable efficacy and have significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge of overcoming intrinsic and acquired resistance in primary and recurrent cancer mediated by EGFR mutations is thus driving the search for alternative strategies in the design of new therapeutic agents. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions.
表皮生长因子受体（EGFR）是表皮生长因子家族成员的受体，调节细胞增殖和信号转导；此外，EGFR 与抑制肿瘤细胞增殖、血管生成、侵袭、转移和凋亡有关。因此，EGFR 已成为癌症治疗的重要靶点，包括非小细胞肺癌、头颈部癌、乳腺癌、脑胶质瘤、宫颈癌和膀胱癌。第一代至第三代 EGFR 抑制剂已显示出相当的疗效，并显著改善了疾病预后。然而，大多数患者在治疗后会产生耐药性。因此，克服由 EGFR 突变介导的原发性和复发性癌症中内在和获得性耐药的挑战，正在推动在新治疗药物的设计中寻找替代策略。鉴于对第三代抑制剂的耐药性，了解耐药性的复杂机制将为开发更先进的靶向治疗提供思路。在这篇综述中，我们讨论了第三代 EGFR 抑制剂耐药的分子机制，并回顾了克服耐药性的最新策略、新挑战和未来的发展方向。
