Scholarlink

<p>Glioblastoma multiforme (GBM) remains one of the most aggressive primary brain tumors with limited therapeutic options. The efficacy of standard temozolomide chemotherapy is critically influenced by O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. While monoclonal antibody (mAb)-based biologics represent a promising therapeutic approach, current clinical trials have failed to demonstrate significant improvement in overall patient survival. In this study, systematic screening identified histamine H1 receptor (HRH1) as a potential therapeutic target. Genetic silencing of HRH1 significantly inhibited GBM cell proliferation, migration, and invasion both in vitro and in vivo. Pharmacological validation using the HRH1-specific antagonist terfenadine confirmed the anti-tumor effects of HRH1 targeting. Based on these findings, we developed an HRH1-targeting mAb that demonstrated potent anti-tumor activity in GBM xenograft models. Mechanistic investigations revealed that the therapeutic effect was mediated through protein kinase C (PKC)-dependent regulation of the RAF/MEK/ERK signaling pathway. In conclusion, we provided a new target, HRH1, for treating GBM and constructed an effective therapeutic mAb.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HRH1-targeting mAb: a precision therapeutic strategy for Glioblastoma

  • 期刊论文

  • 发表日期：

    2025年10月23日

查看全文
  • Kankai Wang,
  • Peiqi Zhao,
  • Xiaohong Zhu,
  • Fan Tang,
  • Hong Chen,
  • Ying Zhang,
  • Hao Wang,
  • Yu Chen,
  • Yuanbo Pan,
  • Qichuan Zhuge,
  • Jianjing Yang

摘要

Glioblastoma multiforme (GBM) remains one of the most aggressive primary brain tumors with limited therapeutic options. The efficacy of standard temozolomide chemotherapy is critically influenced by O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. While monoclonal antibody (mAb)-based biologics represent a promising therapeutic approach, current clinical trials have failed to demonstrate significant improvement in overall patient survival. In this study, systematic screening identified histamine H1 receptor (HRH1) as a potential therapeutic target. Genetic silencing of HRH1 significantly inhibited GBM cell proliferation, migration, and invasion both in vitro and in vivo. Pharmacological validation using the HRH1-specific antagonist terfenadine confirmed the anti-tumor effects of HRH1 targeting. Based on these findings, we developed an HRH1-targeting mAb that demonstrated potent anti-tumor activity in GBM xenograft models. Mechanistic investigations revealed that the therapeutic effect was mediated through protein kinase C (PKC)-dependent regulation of the RAF/MEK/ERK signaling pathway. In conclusion, we provided a new target, HRH1, for treating GBM and constructed an effective therapeutic mAb.