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

Background/AimsLiver cancer ranks third in cancer-related deaths globally, projected to exceed one millionannually by 2030. Existing therapies have significant limitations, including severe sideeffects and inconsistent efficacy. Innovative therapeutic approaches to address primary livercancer (PLC) have led to the ongoing development of tumor-derived organoids. These aresophisticated three-dimensional structures capable of mimicking native tissue architectureand function in vitro, improving our ability to model in vivo homeostasis and disease.MethodsThis systematic review consolidates known literature on human and mouse liver organoidsacross all PLC subtypes, emphasizing diagnostic precision, disease modeling, and drugscreening capabilities.ResultsAcross all 39 included studies, organoids were frequently patient derived organoids (PDO),closely followed by cancer cell line derived organoids (CCO). The literature concentrated onHepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC), whileexploration of other subtypes was limited. These studies demonstrate a valuable role for PLCorganoid cultures in biomarker discovery, disease modeling, and therapeutic exploration.ConclusionsEncouraging advancements such as organoid-on-a-chip and co-culturing systems presentpromising prospects in advancing treatment regimens for PLC. Standardizing in vitroprotocols is crucial to integrate research breakthroughs into practical treatment strategies forPLC.Impact and ImplicationsThis review underscores the expanding utility of PLC organoids across therapeutic discovery,diagnostics, and disease modeling. PDOs replicate many tumor characteristics. Novel genesfrom HCC organoids offer promising biomarkers for personalized treatments. Innovativemethodologies, like microfluidic chips, enhance organoid culture reproducibility. Despitelimitations, co-culturing, and organ-on-a-chip show potential in better mimicking the in vivo tumor microenvironment. These advancements position PLC organoids as crucial tools forpersonalized cancer therapy, biomarker discovery, and disease modeling, with ongoingprotocol standardization efforts essential for clinical applications.<br/