Rui-Kyi Ng, Vishal G Shelat
Carbohydrate antigen 72-4 (CA72-4) is a serum tumor marker linked to tumor-associated glycoprotein 72 (TAG-72), a high-molecular-weight mucin-like antigen identified during the monoclonal-antibody era. Although developed later than CA19-9 and most closely associated with gastric cancer, CA72-4 has since attracted broader interest across gastrointestinal oncology, peritoneal disease, malignant effusions, cytology, benign false-positive states and TAG-72-directed translational research. This review examines the history, biology, clinical utility, diagnostic limitations and future applications of CA72-4 and TAG-72, using gastric cancer as the principal clinical anchor while considering wider esophagogastric, colorectal, appendiceal, pancreaticobiliary, peritoneal and fluid-based applications. Current evidence supports CA72-4 as an adjunctive biomarker rather than a population screening test or stand-alone diagnostic tool. Its most defensible clinical roles are in gastric cancer risk stratification, peritoneal disease assessment, selected multimarker panels and malignant effusion work-up. Looking ahead, TAG-72 may ultimately prove more clinically consequential than serum CA72-4 itself if imaging, cytology-based diagnostics and targeted therapeutic platforms continue to mature.