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

Ayesha A Qureshi, Chase Wehrle, Sofía Ferreira-Gonzalez, Chunbao Jiao, Hanna Hong, Neda Dadgar, Jorge Arpi-Palacios, Yee Phoon Phong, Jaekeun Kim, Keyue Sun, Koji Hashimoto, David CH Kwon, Charles Miller, Nic Leipzig, Wen Wee Ma, Jos Melenhorst, Federico Aucejo, Andrea Schlegel

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 modeling, 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 modeling, 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.
Impact and Implications
This review underscores the expanding utility of PLC organoids across therapeutic discovery,
diagnostics, and disease modeling. PDOs replicate many tumor characteristics. Novel genes
from HCC organoids offer promising biomarkers for personalized treatments. Innovative
methodologies, like microfluidic chips, enhance organoid culture reproducibility. Despite
limitations, 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 for
personalized cancer therapy, biomarker discovery, and disease modeling, with ongoing
protocol standardization efforts essential for clinical applications.
Original languageEnglish
JournalJHEP Reports
DOIs
Publication statusPublished - 1 Jul 2024

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