Neurosurgically-applied chemotherapy for childhood brain tumours arising in the posterior fossa using a biodegradable paste

Medulloblastoma (MB) group 3 and Atypical Teratoid Rhabdoid Tumours (ATRT) represent paediatric brain tumours with a very poor prognosis. Current standard treatment methods are not effective, and we are in need of finding new drug treatments against these tumours. To this end, we have developed a 3D in vitro model which mimics the environment in which cerebellar brain tumours grow. This model consists of commercial paediatric cerebellar brain tumour cell lines (medulloblastoma group 3 and ATRT), healthy brain cells (primary human astrocytes) and a non-diseased human (autopsy) brain derived scaffold for the cells to grow in. Our study aims to grow cells in a more relevant physiological environment to facilitate accurate downstream analysis. We have extracted RNA and protein from the cancer cell lines following 7 days of co-culture with astrocytes and human brain scaffold (extracellular matrix) to study the effects of astrocyte-cancer communication. We have identified many differentially expressed genes following co-culture, which we are now utilising as candidate drug targets predicated on induced pro-survival functions. Our overall aim is to find relevant drug treatments which are effective in surgical resection animal models for these tumours, in which can be rapidly progressed to clinical trials.  Relevant CBTN members will have co-authorship on publications arising from this work and will gain information on these cells following co-culture in a realistic 3D cell culture model.