Organoid Models of Hepatocellular Carcinoma

NCT ID: NCT06929845

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2026-08-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

organoids models

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesca Romana Ponziani, PI

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8

Locations

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8

Roma, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Francesca Romana Ponziani, PI

Role: CONTACT

francescaromana.ponziani@policlinicogemelli.it

3471227242

Elisabetta Creta, SC

Role: CONTACT

elisabetta.creta@policlinicogemelli.it

3480778584

Facility Contacts

Francesca Romana Ponziani

Role: primary

francescaromana.ponziani@policlinicogemelli.it

+393471227242

Other Identifiers

6845

Identifier Type: -

Identifier Source: org_study_id