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<p>Pooled analysis of the SPOTLIGHT and GLOW phase III trials, involving 1072 patients with locally advanced or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma positive for claudin18.2 (CLDN18.2) and negative for HER2, showed that zolbetuximab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo (HR = 0.72; 95% CI, 0.61–0.84). Subgroup analyses revealed better outcomes in Asian patients, those with gastric cancer, and those with intestinal-type GC. In a cohort of 92 GC patients (immunohistochemical detection based on a CLDN18.2 subtype-specific antibody), CLDN18.2 positivity was associated with lymph node metastasis, advanced cancer stages (III–IV), and shorter overall survival (OS) (HR = 1.728; 95% CI, 1.003–2.977; <i>P</i> = 0.0404). In our study, knockdown of CLDN18.2 inhibited tumor growth in vivo and in vitro. Additionally, CLDN18.2 knockdown down-regulated minichromosome maintenance (MCM) proteins, particularly MCM2 and MCM5, and decreased phosphorylation of ERK, CDK, and MCM2 in GC cells. These findings provide a theoretical basis for the future selection of advantageous populations for CLDN18.2-targeted therapy and combination therapy strategies.</p>

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Claudin18.2 promote gastric cancer proliferation by activating MCM2/5

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Bowen Zheng,
  • Miao Fu,
  • Fanzhuoran Lou,
  • Yuting He,
  • Lingying Zhao,
  • Xintian Huang,
  • Xiaowen Xie,
  • Weijuan Tan,
  • Quan Chen,
  • Wenqing Zhang,
  • Yongxiang Hong,
  • Kaiyi Rong,
  • Yuyan Lu,
  • Ping Zhan,
  • Jingke Tu,
  • Huibo Shi,
  • Tianhui Hu,
  • Li Xiao

摘要

Pooled analysis of the SPOTLIGHT and GLOW phase III trials, involving 1072 patients with locally advanced or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma positive for claudin18.2 (CLDN18.2) and negative for HER2, showed that zolbetuximab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo (HR = 0.72; 95% CI, 0.61–0.84). Subgroup analyses revealed better outcomes in Asian patients, those with gastric cancer, and those with intestinal-type GC. In a cohort of 92 GC patients (immunohistochemical detection based on a CLDN18.2 subtype-specific antibody), CLDN18.2 positivity was associated with lymph node metastasis, advanced cancer stages (III–IV), and shorter overall survival (OS) (HR = 1.728; 95% CI, 1.003–2.977; P = 0.0404). In our study, knockdown of CLDN18.2 inhibited tumor growth in vivo and in vitro. Additionally, CLDN18.2 knockdown down-regulated minichromosome maintenance (MCM) proteins, particularly MCM2 and MCM5, and decreased phosphorylation of ERK, CDK, and MCM2 in GC cells. These findings provide a theoretical basis for the future selection of advantageous populations for CLDN18.2-targeted therapy and combination therapy strategies.