Claudine 18.2 : nouvelle cible thérapeutique dans les cancers digestifs

Abstract

Therapies targeting HER2 and immune checkpoint inhibitors have improved survival in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma, but the prognosis associated with these cancers remains poor. Claudin 18.2 is a tight junction protein expressed in the oeso-gastric mucosa. Some gastric and gastro-oesophageal junction adenocarcinoma overexpress this protein, as well as some pancreatic, ovarian and pulmonary cancers. In pathological context, its epitope may be exposed at the surface of cells and therefore makes it an interesting therapeutic target. Zolbetuximab, a monoclonal antibody targeting claudin 18.2, showed a survival benefit in first line metastatic treatment in patients with claudin 18.2 positive gastric and gastro-oesophageal junction adénocarcinoma, in two phase III studies. CAR T-cells specifically targeting this protein have also shown promising efficacy from the second line of treatment. Considering the probable impact of the expression status of claudin 18.2 in future treatment algorithms, this review aims to present the pathophysiology underlying the targeting of claudin 18.2, summarize state of the art results of anti-claudin 18.2 therapies and discuss future challenges for the management of patients with claudin 18.2 positive gastric and gastro-oesophageal junction adenocarcinoma.