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表皮生长因子受体（EGFR）：关于其在肿瘤中的激活与突变及肿瘤免疫治疗的新见解

EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.

作者信息

Gu Yuanzhuo, He Hongchao, Qiao Shilei, Shao Yifan, Wang Lurong, Zhang Zhengkui, Zhang Long, Zhou Fangfang

机构信息

Department of Gynecological Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215006, China.

出版信息

Adv Sci (Weinh). 2025 Sep;12(36):e05785. doi: 10.1002/advs.202505785. Epub 2025 Aug 27.

DOI:10.1002/advs.202505785
PMID:40859900
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12462975/
Abstract

The success of immune checkpoint blockades (ICBs) has accelerated the clinical implementation of multiple single agents and combination immunotherapies, but the response rates vary. Reconsideration of immune-oncology therapeutic failures via perspective from tumor-intrinsic (such as oncogenic driver genes) and tumor-extrinsic (the complexity of immune cell-cancer cell interactions) may help to better design more effective anticancer drugs and treatment strategies. Herein, in this review, introducing the frequently mutated gene EGFR in tumors and its abnormal activation are mainly focused on, highlighting that epidermal growth factor receptor (EGFR) wild-type and mutants respond differently to ICBs via tumor-intrinsic and tumor-extrinsic manners. Through briefly reviewing how EGFR is activated and the current EGFR targeting strategy, the present clinical trials of combination with EGFR inhibitors and ICBs are summarized, and the mechanism by which EGFR affects immunotherapy and measures to improve the efficacy of immunotherapy are discussed.

摘要

免疫检查点阻断（ICB）的成功加速了多种单药和联合免疫疗法的临床应用，但有效率各不相同。从肿瘤内在因素（如致癌驱动基因）和肿瘤外在因素（免疫细胞与癌细胞相互作用的复杂性）的角度重新审视免疫肿瘤治疗失败的情况，可能有助于更好地设计更有效的抗癌药物和治疗策略。在本综述中，主要聚焦于介绍肿瘤中频繁突变的基因EGFR及其异常激活，强调表皮生长因子受体（EGFR）野生型和突变体通过肿瘤内在和外在方式对ICB的反应不同。通过简要回顾EGFR如何被激活以及当前的EGFR靶向策略，总结了目前EGFR抑制剂与ICB联合的临床试验，并讨论了EGFR影响免疫治疗的机制以及提高免疫治疗疗效的措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/34acd09ffa54/ADVS-12-e05785-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/2bbdb3b62b5c/ADVS-12-e05785-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/21bd43f43464/ADVS-12-e05785-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/34acd09ffa54/ADVS-12-e05785-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/e1705c95b17f/ADVS-12-e05785-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/efad401a0c3a/ADVS-12-e05785-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/77d7005f5c51/ADVS-12-e05785-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/d26e468164bf/ADVS-12-e05785-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/2bbdb3b62b5c/ADVS-12-e05785-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/21bd43f43464/ADVS-12-e05785-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b8/12462975/34acd09ffa54/ADVS-12-e05785-g009.jpg

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本文引用的文献

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Decoding the Clinical and Molecular Signatures of EGFR Common, Compound, and Uncommon Mutations in NSCLC: A Brief Report.解读非小细胞肺癌中EGFR常见、复合及罕见突变的临床和分子特征：简要报告
J Thorac Oncol. 2025 Apr;20(4):500-506. doi: 10.1016/j.jtho.2024.12.012. Epub 2024 Dec 16.
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Oncolytic cytomegaloviruses expressing EGFR-retargeted fusogenic glycoprotein complex and drug-controllable interleukin 12.表达表皮生长因子受体（EGFR）重靶向融合糖蛋白复合物和药物可控白细胞介素12的溶瘤巨细胞病毒
Cell Rep Med. 2025 Jan 21;6(1):101874. doi: 10.1016/j.xcrm.2024.101874. Epub 2024 Dec 17.
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Discovery of a molecular glue for EGFR degradation.
发现一种用于表皮生长因子受体（EGFR）降解的分子胶。
Oncogene. 2025 Mar;44(8):545-556. doi: 10.1038/s41388-024-03241-8. Epub 2024 Dec 3.
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Afatinib boosts CAR-T cell antitumor therapeutic efficacy via metabolism and fate reprogramming.阿法替尼通过代谢和命运重编程增强 CAR-T 细胞抗肿瘤治疗效果。
J Immunother Cancer. 2024 Nov 17;12(11):e009949. doi: 10.1136/jitc-2024-009949.
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Nuclear EGFR in breast cancer suppresses NK cell recruitment and cytotoxicity.乳腺癌中的细胞核表皮生长因子受体抑制自然杀伤细胞的募集和细胞毒性。
Oncogene. 2025 Feb;44(5):288-295. doi: 10.1038/s41388-024-03211-0. Epub 2024 Nov 9.
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Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen.非小细胞肺癌中具有 EGFR 外显子 20 插入的肿瘤免疫微环境可能预测一线 ICI 联合治疗方案的疗效。
Lung Cancer. 2024 Sep;195:107933. doi: 10.1016/j.lungcan.2024.107933. Epub 2024 Aug 22.
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Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study.替雷利珠单抗联合西妥昔单抗和伊立替康治疗难治性微卫星稳定和 RAS 野生型转移性结直肠癌的单臂 2 期研究。
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