Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening
Ayesha A. Qureshi,
Chase J. Wehrle,
Sofia 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
Affiliations
Ayesha A. Qureshi
Nationwide Children's Hospital, Abigail Wexner Research Institute, 575 Children's Crossroad, Columbus, OH, 43215, USA
Chase J. Wehrle
Transplantation Center, Cleveland Clinic, OH, USA
Sofia Ferreira-Gonzalez
CIR Centre for Inflammation Research, University of Edinburgh, 5 Little France Drive Edinburgh, EH16 4UU, UK
Chunbao Jiao
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Hanna Hong
Transplantation Center, Cleveland Clinic, OH, USA
Neda Dadgar
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH, USA; Translational Hematology & Oncology Research, Cleveland Clinic, Enterprise Cancer Institute, Cleveland, OH, USA
Jorge Arpi-Palacios
Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH, USA
Yee Phoon Phong
Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH, USA
Jaekeun Kim
Transplantation Center, Cleveland Clinic, OH, USA
Keyue Sun
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Koji Hashimoto
Transplantation Center, Cleveland Clinic, OH, USA
David CH. Kwon
Transplantation Center, Cleveland Clinic, OH, USA
Charles Miller
Transplantation Center, Cleveland Clinic, OH, USA
Nic Leipzig
The University of Akron, Department of Chemical, Biomolecular, and Corrosion Engineering, Akron, OH, USA
Wen Wee Ma
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH, USA
Jos Melenhorst
Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH, USA
Federico Aucejo
Transplantation Center, Cleveland Clinic, OH, USA
Andrea Schlegel
Transplantation Center, Cleveland Clinic, OH, USA; Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Corresponding author. Address: 9500 Euclid Avenue, Cleveland, OH 44195, USA; Tel. (216) 339-0741.
Background & Aims: Liver cancer-related deaths are 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 most frequently patient-derived, closely followed by cancer cell line-derived. The literature concentrated on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, 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 advances such as organoid-on-a-chip and co-culturing systems hold promise for 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 study provides an overview of the current understanding of tumor-derived organoids in primary liver cancers, emphasizing their potential in diagnostics, disease modeling, and drug screening. The scientific foundation rests on the organoids' ability to replicate the tumor microenvironment and genetic landscape, opening new avenues for personalized therapies. These insights are crucial for both researchers and clinicians, as patient-derived organoids can help identify biomarkers and therapeutic targets. Physicians and policymakers can harness these advances to drive progress in precision medicine, while recognizing the challenges involved in standardizing organoid models for clinical implementation.
