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

Area of Science:

• Hepatology and Oncology
• Translational Cancer Research
• Preclinical Model Development

Background:

• Primary liver cancer presents a significant global health burden with poor survival rates.
• Tumor heterogeneity, therapy resistance, and chronic liver disease contribute to poor patient outcomes.
• Current immunotherapies and combination treatments show limited efficacy, highlighting the need for predictive biomarkers.

Purpose of the Study:

• To review and evaluate the strengths and limitations of various patient-derived models for primary liver cancer.
• To identify the challenges and opportunities in developing preclinical models that accurately reflect the liver cancer landscape.
• To emphasize the need for advanced models to facilitate personalized and effective liver cancer treatments.

Main Methods:

• Review of existing literature on patient-derived cell lines (PDCL), 3-D patient-derived tumor organoids (PDTOs), and patient-derived xenografts (PDXs).
• Analysis of the suitability of these models in capturing molecular, cellular, and immune characteristics of primary liver cancer.
• Discussion of ex vivo tissue culture and humanized animal models.

Main Results:

• PDCLs and PDTOs facilitate high-throughput screening but lack a representative tumor microenvironment.
• PDXs, including immune-humanized models, better mimic tumor-environment interactions but are costly and complex.
• Ex vivo cultures preserve tissue architecture and immune interactions but are limited by short viability.

Conclusions:

• No single current patient-derived model fully recapitulates the complexity of primary liver cancer.
• Advancements in multi-cellular 3-D cultures and in vivo humanization are essential.
• Innovative preclinical models are critical for developing personalized and more effective therapies for liver cancer.