[Claudine 18.2: A new therapeutic target in digestive cancers]

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Context:

• Metastatic gastric and gastro-oesophageal junction adenocarcinoma prognosis remains poor despite HER2 and immune checkpoint inhibitor therapies.
• Claudin 18.2, a tight junction protein, is overexpressed in a subset of these adenocarcinomas, as well as pancreatic, ovarian, and pulmonary cancers.
• Claudin 18.2's surface-exposed epitope presents a viable therapeutic target.

Purpose:

• To review the pathophysiology of targeting claudin 18.2.
• To summarize current results of anti-claudin 18.2 therapies.
• To discuss future challenges in managing claudin 18.2-positive gastric and gastro-oesophageal junction adenocarcinoma.

Summary:

• Zolbetuximab, a monoclonal antibody targeting claudin 18.2, demonstrated a survival benefit in first-line metastatic treatment for claudin 18.2-positive gastric and gastro-oesophageal junction adenocarcinoma in two Phase III studies.
• CAR T-cells targeting claudin 18.2 have also shown efficacy from the second-line treatment.
• Claudin 18.2 expression status is likely to influence future treatment algorithms.

Impact:

• Anti-claudin 18.2 therapies offer a new therapeutic avenue for patients with advanced gastric and gastro-oesophageal junction adenocarcinoma.
• Targeting claudin 18.2 may improve survival outcomes for patients with specific cancer types.
• Further research is needed to optimize the management of claudin 18.2-positive cancers.