Serena Pillozzi, Giulia Petroni, Daniele Lavacchi, Daniele Rossini, Lorenzo Antonuzzo
Liquid biopsy (LB) has emerged as a minimally invasive approach to characterize tumor biology and support treatment decision-making across gastrointestinal (GI) malignancies. Advances in circulating biomarkers have expanded its potential clinical applications. While colorectal cancer appears closest to clinical implementation, with ctDNA increasingly integrated into adjuvant and metastatic decision-making, applications in other GI tumors remain largely exploratory. Emerging approaches, including cfDNA methylation profiling, multi-omic assays, and circulating protein or metabolite analyses, have shown promising early signals but require prospective validation. This review summarizes key LB findings presented at ESMO 2025, highlighting translational relevance, current limitations, and future directions for clinical integration.