Epidermal growth factor receptor (EGFR) is a receptor for epithelial growth factor (EGF) cell proliferation and signaling, which is related to the inhibition of tumor cell proliferation, angiogenesis, tumor invasion, metastasis, and apoptosis. Thus, it has become an important target for the treatment of non-small cell lung cancer (NSCLC). The first to the third-generation EGFR inhibitors have demonstrated powerful efficacy and brought a prospect to patients. Unfortunately, after 9-15 months of treatment, they all developed resistance without exception. As for the resistance of third-generation inhibitors, no major breakthrough has been made in this field. In this review, we discussed the recent advances in medicinal chemistry of fourth-generation EGFR-TKIs, as well as further discussed the clinical challenges and future prospects of treating patients with EGFR mutations resistant to third-generation EGFR-TKIs.

表皮生长因子受体（EGFR）是上皮生长因子（EGF）细胞增殖和信号传导的受体，与抑制肿瘤细胞增殖，血管生成，肿瘤侵袭，转移和凋亡有关。因此，它已成为治疗非小细胞肺癌（NSCLC）的重要目标。第一代至第三代EGFR抑制剂已显示出强大的功效，并为患者带来了希望。不幸的是，经过9-15个月的治疗，他们全都出现了抵抗力。至于第三代抑制剂的抗性，在该领域没有重大突破。在这篇综述中，我们讨论了第四代EGFR-TKI药物化学的最新进展，