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Updated: Aug 15, 2025

Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
Identification and functional characterization of potential oncofetal targets in human hepatocellular carcinoma
Mei-Mei Li1, Fan-En Kong1, Guang-Meng Li2
1Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China.
Abstract:
Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC. For complete details on the use and execution of this protocol, please refer to Kong et al. (2021).1.
Insights
This study outlines a protocol to identify oncofetal targets for hepatocellular carcinoma (HCC) by using cell models and xenografts. It also details developing antibody therapeutics targeting tumor plasticity in HCC.
Area of Science:
- Oncology
- Cell Biology
- Drug Development
Background:
- Hepatocellular carcinoma (HCC) presents challenges in targeted therapy.
- Tumor lineage plasticity is a key mechanism in HCC progression and drug resistance.
- Identifying novel oncofetal targets is crucial for effective HCC treatment.
Purpose of the Study:
- To present a detailed protocol for identifying potential oncofetal targets in hepatocellular carcinoma (HCC).
- To describe methods for developing antibody-based therapeutics targeting tumor lineage plasticity in HCC.
Main Methods:
- Utilized a hepatocyte differentiation model and a sorafenib-refractory cell-line-derived xenograft model.
- Established procedures for tumor sphere formation, organoid generation, and subcutaneous tumor formation.
- Employed immunohistochemistry and immunofluorescence to analyze lineage-specific marker expression.
Main Results:
- Successfully developed a comprehensive protocol for oncofetal target identification in HCC.
- Demonstrated the feasibility of generating functional models for studying HCC.
- Laid the groundwork for developing novel antibody-based therapeutics.
Conclusions:
- The presented protocol enables the identification of critical oncofetal targets in HCC.
- This approach facilitates the development of targeted therapies addressing tumor lineage plasticity.
- The study provides a robust framework for advancing HCC therapeutic strategies.
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