A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma.
10.1007/s11684-022-0945-y
- Author:
Jing YANG
1
;
Yanfei YANG
1
;
Yuquan WEI
1
;
Xiawei WEI
2
Author Information
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. 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. xiaweiwei@scu.edu.cn.
- Publication Type:Journal Article
- Keywords:
ErbB receptors;
HM781-36B;
cisplatin;
epidermal growth factor receptor;
molecular targeted therapy;
nasopharyngeal carcinoma
- MeSH:
Humans;
Animals;
Mice;
Cisplatin/therapeutic use*;
Antineoplastic Agents/therapeutic use*;
Nasopharyngeal Carcinoma/drug therapy*;
Mice, Nude;
Nasopharyngeal Neoplasms/pathology*;
Tumor Microenvironment
- From:
Frontiers of Medicine
2023;17(2):275-289
- CountryChina
- Language:English
-
Abstract:
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.
