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Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates
Journal article   Open access   Peer reviewed

Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates

Kelley Weinfurtner, Rudra Amin, Nicolas Skuli, Terence P. Gade and David E. Kaplan
Seminars in liver disease, v 46(1), pp 51-62
01 Mar 2026
PMID: 41534869
url
https://doi.org/10.1055/a-2779-4984View
Published, Version of Record (VoR) Open CC BY V4.0

Abstract

cholangiocarcinoma hepatocellular carcinoma organoids patient-derived models patient-derived xenograft
Primary liver cancer remains a global health challenge due to rising incidence, limited curative options, and poor overall survival. Poor outcomes stem from tumor heterogeneity, limited efficacy of current therapies, and comorbid chronic liver disease. Despite recent advances in immunotherapy and combination treatments, response rates remain low, and predictive biomarkers are lacking. As a result, there is an urgent need for preclinical models that capture the molecular, cellular, and immune landscape of primary liver cancer. This review discusses the strengths and limitations of patient-derived models of liver cancer, including two-dimensional patient-derived cell lines (PDCL), three-dimensional (3D) patient-derived tumor organoids (PDTOs), and patient-derived xenografts (PDXs). While PDCLs and PDTOs enable high throughput studies, they lack a representative tumor microenvironment. PDXs, including PDXs in animals with humanized immune systems, may more effectively mimic tumor–environment interactions but are costly, complex, and still contain mouse stromal cells. Ex vivo tissue culture preserves tissue structure and cell–cell interactions in an immunocompetent environment; however, short duration of viable culture limits broader application. Continued innovation in the development of multicellular three-dimensional culture systems and in vivo humanization strategies will play a critical role in enabling the development of more personalized and effective therapies for primary liver cancer.

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Collaboration types
Domestic collaboration
Web of Science research areas
Gastroenterology & Hepatology
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