Organoid Models of Hepatocellular Carcinoma

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Enrolling

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

Treatments: Procedure: organoids models

Study type: Interventional

Funder types: Other

Identifiers

NCT06929845

6845

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 1 patient group

HCC organoid models development

Experimental group

Description:

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

Treatment:

Procedure: organoids models