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<p>Systemic chemotherapy remains the standard treatment for advanced gastroesophageal cancer, typically combining a&#xa0;fluoropyrimidine with oxaliplatin. Despite recent advances through biomarker-driven therapies, overall prognosis remains poor. Claudin 18.2, a&#xa0;tight junction protein aberrantly exposed on tumor cells, has emerged as a&#xa0;novel therapeutic target. The phase&#xa0;III SPOTLIGHT and GLOW trials demonstrated improved survival outcomes with zolbetuximab, an anti-claudin 18.2 monoclonal antibody, combined with chemotherapy in patients with claudin 18.2-positive tumors. This review summarizes the biological role of claudin 18.2, current clinical trial evidence, integration of zolbetuximab into treatment algorithms, and considerations regarding its safety and impact on quality of life.</p>

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Zolbetuximab and the novel biomarker claudin 18.2 in the treatment of gastroesophageal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月11日

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  • Aysegül Ilhan-Mutlu,
  • Florian Lordick,
  • Ewald Wöll

摘要

Systemic chemotherapy remains the standard treatment for advanced gastroesophageal cancer, typically combining a fluoropyrimidine with oxaliplatin. Despite recent advances through biomarker-driven therapies, overall prognosis remains poor. Claudin 18.2, a tight junction protein aberrantly exposed on tumor cells, has emerged as a novel therapeutic target. The phase III SPOTLIGHT and GLOW trials demonstrated improved survival outcomes with zolbetuximab, an anti-claudin 18.2 monoclonal antibody, combined with chemotherapy in patients with claudin 18.2-positive tumors. This review summarizes the biological role of claudin 18.2, current clinical trial evidence, integration of zolbetuximab into treatment algorithms, and considerations regarding its safety and impact on quality of life.