Novel Liquid Biopsy in Gastrointestinal Cancers

Gastrointestinal (GI) cancers represent a significant global health burden, being among the leading causes of cancer-related deaths. The prognosis for patients remains unsatisfactory, largely because most cancers are detected at advanced stages. Traditional diagnostic methods, such as radiological and histopathological examinations and serum tumor markers like AFP, CEA, CA-125, and CA-199, possess limitations in sensitivity and specificity, particularly for early screening. A major drawback of tissue biopsy is its inability to fully capture the inherent heterogeneity within tumors, as mutations can differ between primary and metastatic sites. In this context, liquid biopsy has emerged as a promising, minimally invasive alternative for detecting cancer-associated materials present in various body fluids. The concept of liquid biopsy, initially centered on circulating tumor cells, has expanded to encompass other critical biomarkers such as circulating tumor DNA, extracellular vesicles, and circulating tumor RNA. Analyzing these biomarkers using advanced techniques like next-generation sequencing or proteomics can unveil a wealth of potential information. Liquid biopsy offers numerous advantages, being less invasive, more convenient, potentially more cost-effective, and providing a dynamic, real-time snapshot of the entire tumor burden that reflects both intertumoral and intratumoral heterogeneity. This review provides an overview of key liquid biopsy biomarkers and their associated detection technologies, discusses their burgeoning clinical applications across various GI cancer types, and highlights the current challenges and future directions in this rapidly evolving field.