Organoid Models of Hepatocellular Carcinoma

Organoid Models of Hepatocellular Carcinoma to Test Treatment Efficacy, Exploring Correlations With Tumor Microenvironment and Gut-liver-tumor Axis.

A promising tool to elucidate the molecular characteristics of HCC are patient-derived organoids (PDOs), three-dimensional cultures of cells that self-organise according to tissue-specific patterns and can be used to test the susceptibility of a specific tumour to anticancer agents. In this study, PDOs for HCC will be developed that closely resemble the tumour microenvironment in vivo and mimic the crosstalk of the gut-liver axis to establish a correlation with patient prognosis and test the efficacy of available systemic therapies.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Surgery; Gut Microbiota; Organoids; Tumor Microenvironment; System Disorders, Digestive
• Intervention / Treatment: Procedure: organoids models

Detailed Description

The objectives of the project will be 1) to develop HCC PDOs from tumour and non-tumour patient liver tissue obtained from surgical specimens or liver biopsies; 2) to evaluate genomic and transcriptomic changes resulting from the integration of HCC PDOs with patient-derived gut microbiota and host immune cells, and to assess the correlation with patient prognosis; 3) to exploit HCC PDOs to test the efficacy of systemic therapies (ICI and TKIs) and to understand possible modifying cofactors.

Researchers with laboratory experience have been recruited who will focus on the construction of PDOs and the analysis of immune-inflammatory pathways. State-of-the-art technologies will be used, in particular next-generation sequencing, flow cytometry, high-throughput genomic and transcriptomic analysis, ultrafiltration, drug screening, multiplex immunoassays and enzyme immunoassays. The project aims to study the mechanisms involved in the modulation of therapeutic efficacy in patients with HCC. Therefore, the experimental model could be a valuable support to be integrated into real clinical practice to maximise therapeutic efficacy through a fully customised strategy.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francesca Romana Ponziani, PI; Phone Number: 3471227242; Email: francescaromana.ponziani@policlinicogemelli.it
• Study Contact Backup: Name: Elisabetta Creta, SC; Phone Number: 3480778584; Email: elisabetta.creta@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8
    • Contact: Francesca Romana Ponziani; Phone Number: +393471227242; Email: francescaromana.ponziani@policlinicogemelli.it
    • Principal Investigator: Francesca Romana Ponziani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Capacity to express informed consent;
• Age ≥18 years;
• Suspected radiological diagnosis of HCC or diagnosis of HCC with indications for surgical resection.

Exclusion Criteria:

• Age < 18 years;
• Contraindications to liver biopsy (ascites, platelets<50,000, INR>1.7);
• Contraindications to HCC resection surgery;
• Active viral infection;
• Refusal to sign informed consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HCC organoid models development; The aim of the present project is to develop a HCC organoid model that closely resembles the in vivo immunological microenvironment, including the contribution of the gut-liver axis. These reconstituted HCC models will then allow us to test tumor sensitiv

Procedure: organoids models; Enrolled patients will undergo liver biopsy with sampling of tumor tissue and adjacent nontumor liver parenchyma. Alternatively, patients who are candidates for surgical resection of HCC will be enrolled. The tumor tissue obtained will be used partly for histological confirmation of HCC and then included in kerosene, partly used for organoid construction, and the nontumor tissue will be used solely for organoids. Genomic and transcriptomic changes resulting from the integration of PDO of HCC with the gut microbiota and host immune cells derived from the patient will be evaluated. In addition, PDOs from HCC will be tested for the efficacy of systemic therapies (ICI and TKI) and understand possible modifying co-factors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organoid model development	The primary endpoint of this study is to assess the correlation between the genomic and histological characteristics of patient-derived organoids (PDOs) from hepatocellular carcinoma (HCC) surgical biopsies and clinical outcomes, specifically disease-free survival (DFS) and overall survival (OS).	2-18 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Francesca Romana Ponziani, PI, Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Digestive System Diseases; Carcinoma, Hepatocellular
• Other Study ID Numbers: 6845

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No