Project description
Innovative lung metastasis-on-a-chip model for osteosarcoma
Osteosarcoma, a highly aggressive bone cancer primarily affecting children, poses a significant threat, particularly due to secondary lung metastasis. Alarmingly, 70 % of individuals developing lung metastasis succumb to the disease within 3 years and treatment protocols have remained largely unchanged since the 1970s. The ERC-funded META-CHIP project aims to develop a lung metastasis-on-a-chip model specifically for osteosarcoma. The approach involves creating patient-derived tumour spheroids (PDTS), offering a superior drug development model compared to traditional cell culture models by more accurately replicating the primary tumour. Furthermore, META-CHIP will develop an osteosarcoma-on-a-chip device to provide a more realistic tumour microenvironment model. Ultimately, the goal is to establish a cost-effective, human systemic model of osteosarcoma metastasis.
Objective
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.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
4 Dublin
Ireland