论文标题：A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma

期刊： Frontiers of Medicine

作者：Jing Yang, Yanfei Yang, Yuquan Wei, Xiawei Wei

发表时间： 15 Apr 2023

DOI：10.1007/s11684-022-0945-y

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四川大学华西医院魏霞蔚等在Frontiers of Medicine发表研究论文《小分子泛HER抑制剂单独使用或与顺铂联合使用治疗鼻咽癌的疗效研究》（A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma）。本研究发现HER家族蛋白在部分鼻咽癌患者肿瘤组织中高表达且与预后不良相关。新型泛HER抑制剂HM781-36B的单独使用能抑制癌细胞增殖、诱导凋亡等，而与顺铂联合使用有协同抗肿瘤的作用。

The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.

人表皮生长因子受体（HER）家族激酶活性的异常激活与人类恶性肿瘤的发生发展密切相关。本研究以HER激酶作为鼻咽癌（NPC）的治疗靶点，探究了新型泛HER抑制剂HM781-36B单独使用或与顺铂联合使用时的抗肿瘤作用。研究发现，部分NPC患者肿瘤组织中HER家族蛋白呈阳性表达，且其高表达水平与患者不良预后显著相关。HM781-36B在体外和体内实验中均能抑制NPC的发展。HM781-36B与顺铂联用可协同抑制NPC细胞增殖并促进其凋亡。在裸鼠NPC移植瘤模型中，HM781-36B与顺铂具有协同抑制肿瘤的效果。下调HER家族蛋白及其下游信号通路的活性，以及调节肿瘤微环境可能是二者协同抗肿瘤的作用机制。综上所述，本研究为将HER家族蛋白作为鼻咽癌的预后生物标志物和潜在治疗靶点提供了依据。泛HER抑制剂HM781-36B单独使用或与顺铂联合使用为NPC患者提供了新的治疗选择，为NPC的综合治疗提供了新思路。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma

作者

Jing Yang^1,2,3, Yanfei Yang^1,4, Yuquan Wei¹, Xiawei Wei¹

机构

1. Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China

2. Melanoma and Sarcoma Medical Oncology Unit, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

4. Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha 410008, China

通讯作者

Xiawei Wei

引用这篇文章

Jing Yang, Yanfei Yang, Yuquan Wei, Xiawei Wei. A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma. Front. Med., 2023, 17(2): 275–289

https://doi.org/10.1007/s11684-022-0945-y

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-022-0945-y

https://link.springer.com/article/10.1007/s11684-022-0945-y

感谢作者对Frontiers of Medicine的信任和支持。

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