Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Simple Summary Gastric cancer is a major global health issue, ranking among the top causes of cancer-related deaths. Unfortunately, most patients are diagnosed in advanced stages, with only a 6% chance of surviving five years. Current treatment involves a specific drug combination, but predicting its effectiveness is challenging. This review explores the changing world of gastric cancer markers, focusing on Claudin 18.2 (CLDN18.2) as a promising target. Recent trials show that Zolbetuximab, a CLDN18.2-targeting drug, works well with chemotherapy for CLDN18.2-positive gastric cancer. Understanding how to choose these therapies is crucial as this new approach unfolds. This review aims to overview new strategies in managing CLDN18.2 positive advanced gastric cancer.Abstract Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.