Lifetime Metabolomics for Paediatric Liver Cancer Detection and Therapy Assessment Using Organ-on-Chip Platforms

Introduction

Understanding cancer metabolism at the individual patient level is central to making accurate early-stage diagnoses and providing effective patient-specific treatments. While some methods do exist to study intra-cell metabolomics and inter-cell metabolic flux alterations (e.g., PET, MRI), their scalability and sensitivity is limited, hindering reliable investigations long-term.

Project Overview

LIFETIME aims to develop a single platform for "lifetime metabolomics," where the metabolic fingerprint of a disease is traced throughout patient onset in vivo, analysis ex vivo, and through to treatment.

Technological Approach

Technologically, this involves rapid metabolomic profiling of the cancer model, using:

1. Microfluidic 3D-cell-cultures in organ-on-chip (OoC) structures
2. Magnetic resonance spectroscopic imaging (MRSI)

Scientific Focus

Scientifically, the disease-specific case study chosen is hepatoblastoma (HB), the most common liver cancer in children, where the platform could improve patient survival rate and quality of life.

Methodology

Metabolic contrast in three phenotypes of HB mouse models (intrahepatic, intravenous, subcutaneous) and their OoC counterparts will be assessed.

Unique Benefits

A unique benefit of the platform will be its capability for parallel, repeatable measurements on samples to track therapeutic-induced metabolic alterations over time. This will unveil tumors' detailed molecular phenotypes and shed light on their correlation with tumor heterogeneity and interactions within the tumor microenvironment.

Long-term Goals

Overall, LIFETIME will enable the definition of new reliable biomarkers of HB that propel the development of targeted therapies. If successful, the scalability of the platform will hold the important ability to bridge in vivo and in vitro assessment, from biopsy-derived cell cultures (parallelized screening) to patients (correlating with current clinical MRSI).

Future Implications

Long term, LIFETIME will empower assessment of the benefits and constraints of OoC technology in cancer and other aggressive disease research.