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

doi:10.1016/j.jhepr.2024.101164

Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening

JHEP Rep. 2024 Jul 1;6(12):101164. doi: 10.1016/j.jhepr.2024.101164. eCollection 2024 Dec.

Authors

Ayesha A Qureshi¹, Chase J Wehrle², Sofia Ferreira-Gonzalez³, Chunbao Jiao⁴, Hanna Hong², Neda Dadgar^{5

6}, Jorge Arpi-Palacios⁷, Yee Phoon Phong⁷, Jaekeun Kim², Keyue Sun⁴, Koji Hashimoto², David Ch Kwon², Charles Miller², Nic Leipzig⁸, Wen Wee Ma⁵, Jos Melenhorst⁷, Federico Aucejo², Andrea Schlegel^{2

4}

Affiliations

¹ Nationwide Children's Hospital, Abigail Wexner Research Institute, 575 Children's Crossroad, Columbus, OH, 43215, USA.
² Transplantation Center, Cleveland Clinic, OH, USA.
³ CIR Centre for Inflammation Research, University of Edinburgh, 5 Little France Drive Edinburgh, EH16 4UU, UK.
⁴ Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁵ Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH, USA.
⁶ Translational Hematology & Oncology Research, Cleveland Clinic, Enterprise Cancer Institute, Cleveland, OH, USA.
⁷ Cleveland Clinic Foundation, Lerner Research Institute, Center for Immunotherapy and Precision Immuno-Oncology, Cleveland, OH, USA.
⁸ The University of Akron, Department of Chemical, Biomolecular, and Corrosion Engineering, Akron, OH, USA.

Abstract

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.

Keywords: 3D cell culture; biomarker; cholangiocarcinoma; diagnosis; drug; gene expression; hepatocellular carcinoma; liver cancer; organoid; therapy.