| Project Detail |
Platform for personalised disease metabolomics from diagnosis to treatment The body continuously produces a tremendous variety of small molecules called metabolites in the process of breaking down and building up molecules. Metabolites are important markers of health and disease. Current approaches to study intracell and intercell metabolomics – the large-scale study of metabolites – in cancer to support personalised medicine is limited. The ERC-funded LIFETIME project aims to develop an organ-on-chip platform able to trace the metabolomic fingerprint of a disease from patient onset in vivo through to treatment. Using hepatoblastoma as a development model, the platform will enable parallel, repeatable measurements over time, revealing details about tumour phenotypes and the tumour microenvironment over time, and enabling the identification of new biomarkers. 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. 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. Technologically this involves rapid metabolomic profiling of the cancer model, using microfluidic 3D-cell-cultures in organ-on-chip (OoC) structures and magnetic resonance spectroscopic imaging (MRSI). 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. Metabolic contrast in three phenotypes of HB mouse models (intrahepatic, intravenous, subcutaneous) and their OoC counterparts will be assessed. 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 tumours detailed molecular phenotypes and shed light on their correlation with tumour heterogeneity and interactions within tumour microenvironment. 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 (parallelised screening) to patients (correlating with current clinical MRSI). Long term, LIFETIME will empower assessment of the benefits and constraints of OoC technology in cancer and other aggressive disease research. |
