Modelling metastasis in 3D: from pathway discovery towards targeted drugs
Dr O Piskareva
Prof J Prehn
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Paediatric cancer research in general and neuroblastoma, in particular,has very limited preclinical models of metastasis. Keeping in mind that 50% of primary neuroblastomas have already metastasised at the time of diagnosis it is paramount to seek new technological and methodological approaches to understand molecular mechanisms underlying this phenomenon.
We aim to model and characterise invasion in 3D tissue-engineered platform that consists of extracellular matrix (ECM) - based hydrogels functionalised to act as 3D structural scaffold supporting neuroblastoma organoids to grow and respond to stimuli in a well-defined environment. We will use PDX-derived organoids to maintain native tumour heterogeneity and invasion phenotypes that can lead to pathway discovery and target validation. Towards this aim, we are taking an integrated approach that combines biological research, molecular and RNA profiling, mathematical modelling and tissue engineering.
By the end of the project, we will greatly advance our understanding of mechanisms of invasion and metastasis of neuroblastoma and contribution of its microenvironment to the process which may be further utilised in the development of effective targeted therapies for children with this disease. The project is pioneering a new area of paediatric cancer research both in Ireland and the International neuroblastoma research community.