SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs
文献类型：期刊论文
| 作者 | Li, Wen-jing1,2; Xie, Cheng-ying1 ; Zhu, Xi1; Tang, Jiao1; Wang, Lei1; Lou, Li-guang1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2024-01-10 |
| 页码 | 10 |
| ISSN号 | 1671-4083 |
| 关键词 | SIBP-03 HER3 HER3-targeted therapy neuregulin 1 EGFR HER2 |
| DOI | 10.1038/s41401-023-01221-4 |
| 通讯作者 | Wang, Lei(wanglei@simm.ac.cn) ; Lou, Li-guang(lglou@simm.ac.cn) |
| 英文摘要 | HER3 (human epidermal growth factor receptor 3) acts through heterodimerization with EGFR (epidermal growth factor receptor) or HER2 to play an essential role in activating phosphoinositide 3-kinase (PI3K) and AKT signaling-a crucial pathway that promotes tumor cell survival. HER3 is a promising target for cancer therapy, and several HER3-directed antibodies have already entered into clinical trials. In this study we characterized a novel anti-HER3 monoclonal antibody, SIBP-03. SIBP-03 (0.01-10 mu g/mL) specifically and concentration-dependently blocked both neuregulin (NRG)-dependent and -independent HER3 activation, attenuated HER3-mediated downstream signaling and inhibited cell proliferation. This antitumor activity was dependent, at least in part, on SIBP-03-induced, cell-mediated cytotoxicity and cellular phagocytosis. Importantly, SIBP-03 enhanced the antitumor activity of EGFR- or HER2-targeted drugs (cetuximab or trastuzumab) in vitro and in vivo. The mechanisms underlying this synergy involve increased inhibition of HER3-mediated downstream signaling. Collectively, these results demonstrated that SIBP-03, which is currently undergoing a Phase I clinical trial in China, may offer a new treatment option for patients with cancers harboring activated HER3, particularly as part of a combinational therapeutic strategy. |
| WOS关键词 | KINASE INHIBITORS ; PHOSPHATIDYLINOSITOL 3-KINASE ; RECEPTOR HETERODIMERIZATION ; GROWTH-FACTOR ; CANCER ; HER3 ; EXPRESSION ; RESISTANCE ; HEREGULIN ; ERBB3 |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[18DZ2293200] ; Yunnan Province Sciences and Technology plan[202102AA310026] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | NATURE PUBL GROUP |
| WOS记录号 | WOS:001139302000002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308523]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Lei; Lou, Li-guang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Wen-jing,Xie, Cheng-ying,Zhu, Xi,et al. SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs[J]. ACTA PHARMACOLOGICA SINICA,2024:10. |
| APA | Li, Wen-jing,Xie, Cheng-ying,Zhu, Xi,Tang, Jiao,Wang, Lei,&Lou, Li-guang.(2024).SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs.ACTA PHARMACOLOGICA SINICA,10. |
| MLA | Li, Wen-jing,et al."SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs".ACTA PHARMACOLOGICA SINICA (2024):10. |
入库方式： OAI收割
来源：上海药物研究所
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