[Oesogastric cancer - new therapeutic targets]

Abstract

The median overall survival of metastatic esophagogastric adenocarcinoma is approximately twelve months. In fifteen years, major breakthrough have been the targeting of HER2 overexpression and more recently immunotherapy in patients with CPS≥5. Recent advances in molecular biology have identified some molecular alterations in esophageal adenocarcinoma, interesting to target. FGFR2 is overexpressed in one third of patients, and its targeting with a specific monoclonal antibody bemarituzumab showed a significant improvement in survival. Claudin 18.2 (CLDN 18.2) is overexpressed in at least a third of esophagogastric adenocarcinomas. The combination of zolbetuximab and chemotherapy provides a survival benefit, correlated with the intensity of CLDN 18.2 expression. The potential interest of targeting other pathways is under investigation in several trials with some encouraging preliminary data, and early trials in these indications, justifying considering large molecular screening in patients who might be candidate for early phase trial. Finally, with the recent advent of immunotherapy, one of the future challenges will be to optimize it through combination strategies with targeted therapies. The combination of anti-angiogenic and immunotherapy seems promising in gastric cancer.

Keywords: Adénocarcinome œsogastrique; Altération moléculaire; Claudin 18.2; Claudine 18.2; FGFR; Molecular alteration; Oesogastric adenocarcinoma; Sequencing; Séquençage; Targeted therapy; Thérapie ciblée.