Tumor Organoids for Primary Liver Cancers: A Systematic Review of Current Applications in Diagnostics, Disease Modeling, and Drug Screening

Background/Aims Liver cancer ranks third in cancer-related deaths globally, projected to exceed one million annually by 2030. Existing therapies have significant limitations, including severe side effects and inconsistent efficacy. Innovative therapeutic approaches to address primary liver cancer (PLC) have led to the ongoing development of tumor-derived organoids. These are sophisticated three-dimensional structures capable of mimicking native tissue architecture and function in vitro, improving our ability to model in vivo homeostasis and disease. Methods This systematic review consolidates known literature on human and mouse liver organoids across all PLC subtypes, emphasizing diagnostic precision, disease modelling, and drug screening capabilities. Results Across all 39 included studies, organoids were frequently patient derived organoids (PDO), closely followed by cancer cell line derived organoids (CCO). The literature concentrated on Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC), while exploration of other subtypes was limited. These studies demonstrate a valuable role for PLC organoid cultures in biomarker discovery, disease modelling, and therapeutic exploration. Conclusions Encouraging advancements such as organoid-on-a-chip and co-culturing systems present promising prospects in advancing treatment regimens for PLC. Standardizing in vitro protocols is crucial to integrate research breakthroughs into practical treatment strategies for PLC.