Organoid Models of Hepatocellular Carcinoma

Not Applicable

Recruiting

• Conditions: Hepatocellular Carcinoma; Organoids; Surgery; Gut Microbiota; Tumor Microenvironment; System Disorders, Digestive

• Registration Number: NCT06929845
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-07-16
• Study Start: 2024-10-01
• Status Verified: 2025-03
• Study First Submitted QC: 2025-04-15
• Last Update Submitted: 2025-04-15
• Study First Posted: 2025-04-16
• Last Update Posted: 2025-04-16
• Primary Completion: 2025-09-01
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Organoid model development	2-18 months	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).

Trial Locations

Locations (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8; 🇮🇹 Roma, Italy