Description du projet
Un modèle innovant de métastases pulmonaires sur puce pour l’ostéosarcome
L’ostéosarcome, un cancer des os très agressif qui touche principalement les enfants, constitue une menace considérable, principalement en raison des métastases pulmonaires secondaires. Il est alarmant de constater que 70 % des personnes qui développent des métastases pulmonaires succombent à la maladie dans les trois ans et que les protocoles de traitement sont restés pratiquement inchangés depuis les années 1970. Le projet META-CHIP, financé par le CER, entend développer un modèle de métastase pulmonaire sur puce spécifique à l’ostéosarcome. Son approche consiste à créer des sphéroïdes tumoraux dérivés de patients (PDTS), qui constituent un modèle de développement de médicaments supérieur aux modèles de culture cellulaire traditionnels qui reproduisent plus fidèlement la tumeur primaire. META-CHIP développera également un dispositif d’ostéosarcome sur puce afin de fournir un modèle de microenvironnement tumoral plus réaliste. À terme, l’objectif est d’établir un modèle systémique humain rentable de métastases d’ostéosarcome.
Objectif
Osteosarcoma is a highly aggressive bone cancer that primarily affects children. Secondary lung metastasis is the most critical clinical factor, with 70% of those who develop lung metastasis succumbing to the disease within 3 years. Despite the resonating clinical urgency for newer, more effective treatment options, there have been no changes in treatment since the introduction of chemotherapy in the 1970s. Furthermore, osteosarcoma is a rare disease making the conduct of large clinical trials investigating novel therapies very challenging. META-CHIP proposes to embark upon frontier research by being the first to develop a lung metastasis-on-a-chip model for osteosarcoma, for use by both the research community and the pharmaceutical industry. This will be realized by first testing the hypothesis that patient derived tumour spheroids (PDTS) generated from patient biopsies will recapitulate the primary tumour and thus be a superior drug development model than traditional cell culture models (Aim 1). An osteosarcoma-on-a-chip device will be developed integrating PDTS, microfluidic technology, and novel biomaterial design to provide a more accurate model of the tumour microenvironment (Aim 2). To validate the device, the ability to predict clinical outcomes on tumour growth following treatment with two anti-angiogenic drugs, which have progressed to Phase II clinical trials will be assessed (Aim 3). Finally, META-CHIP will develop a much-needed platform which mimics key aspects of osteosarcoma metastatic disease progression to the lung. This will be achieved through functional-coupling of the osteosarcoma-on-a-chip device with an established lung-chip to create a medium-throughput, cost-effective, human systemic model of osteosarcoma metastasis (Aim 4). META-CHIP has the potential to revolutionise drug development and treatment of osteosarcoma patients by being the first ex vivo testing platform capable of predicting a patient’s response to therapies in real-time.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
4 Dublin
Irlande