Liquid biopsy for gastric cancer: Techniques, applications, and future directions

Abstract

After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist’s perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

Keywords: Liquid biopsy; Gastric cancer; Circulating tumor cells; Cell-free DNA; Circulating tumor DNA; Molecular

Core Tip: Liquid biopsy (LB) has the potential to revolutionize cancer diagnostics, offering reduced invasiveness and improved understanding of tumor heterogeneity. Going beyond examining circulating tumor cells and cell-free DNA in blood, LB studies now explore a variety of structures and non-blood samples. Despite advancements in LB for tumor detection, prognostic assessment and treatment guidance, challenges remain, including complex and expensive techniques, lack of standardization, and suboptimal scientific evidence. In the context of gastric cancer, LB represents a promising approach, especially in advanced stages. This review navigates through LB intricacies, emphasizing its benefits while urging for future improvements to achieve clinical impact.