Expanding therapeutic options targeting claudin-18.2

The Lancet Oncology Pub Date : 2025-01-06 DOI:10.1016/s1470-2045(24)00710-1

Katharine Herbert, Elizabeth C Smyth

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Abstract

Therapeutic options for patients with advanced gastric or gastro-oesophageal junction adenocarcinomas are rapidly evolving.¹ Although chemotherapy alone results in a median survival of less than a year, the majority (approximately 75%) of gastric and gastro-oesophageal junction adenocarcinoma tumours express molecular targets that are amenable to personalised antibody-based therapies.² These targeted treatments, if combined with cytotoxic chemotherapy, extend overall survival. Established monoclonal antibody targets include HER2 (also known as ERBB2) and PD-L1, with claudin-18.2 (CLD18.2) emerging as an addition within the past year. Zolbetuximab, a first-in-class monoclonal antibody targeting CLD18.2, improved overall survival when added to platinum-fluoropyrimidine chemotherapy in patients with CLD18.2-positive, advanced, untreated gastric or gastro-oesophageal junction adenocarcinoma.³ The positive results of SPOTLIGHT and GLOW validate CLD18.2 as a therapeutic target and established a basis for an expansive pipeline of next-generation CLD18.2-directed therapies.4, 5

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扩展靶向claudin-18.2的治疗选择

晚期胃或胃-食管交界处腺癌患者的治疗选择正在迅速发展虽然单独化疗的中位生存期不到一年，但大多数（约75%）的胃和胃-食管交界处腺癌肿瘤表达的分子靶标可适用于个体化抗体治疗如果结合细胞毒性化疗，这些靶向治疗可以延长总生存期。已建立的单克隆抗体靶点包括HER2（也称为ERBB2）和PD-L1， claudin-18.2 （CLD18.2）是在过去一年中新加入的。Zolbetuximab是一种针对CLD18.2的单克隆抗体，在CLD18.2阳性、晚期、未经治疗的胃或胃-食管交界腺癌患者的铂-氟嘧啶化疗中加入Zolbetuximab可提高总生存率SPOTLIGHT和GLOW的阳性结果验证了CLD18.2作为治疗靶点，并为下一代CLD18.2定向治疗的广泛管道奠定了基础。4、5

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来源期刊

The Lancet Oncology

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