We developed a physiologically relevant in vitro 3D model to find new treatments for paediatric brain cancer. By co-culturing cancer stem cells with brain organoids, we aim to study the pathogenesis of diffuse midline glioma and understand how ellmicroenvironment interactions affect cancer development and invasion. Our model provides an invaluable reclinical platform to identify treatments that effectively kill cancer cells while minimizing neurotoxicity.
Paediatric brain tumours are the most common solid tumour in children, and among them paediatric high-grade gliomas are the deadliest. Current therapies are inadequate, and resultingly these tumours are uniformly fatal. This research aims to advance our understanding of tumour biology to identify new therapies for these devastating diseases. Furthermore, this platform has the potential to be applied to study and find a cure for other brain cancers.
We developed a 3D cancer-brain organoid model and are currently studying the cancer cell growth, migration and invasion on the whole 3D model. We will then perform single-cell gene expression and functional analysis to investigate the biology of cancer cells and evaluate the alterations induced in the cancer microenvironment. Finally, we will develop an in vitro screening platform based on 3D cancer-brain model to find effective drugs for diffuse midline glioma.
The image shows an organoid modeling the cerebral cortex being invaded by human cancer cells. Human cancer cells (red), MAP2-expressing neurons (green) and cell nuclei labelled with DAPI (blue) in a whole 3D model grown for 53 days.
Dr Maria Giovanna Garone, Neural Stem Cell group (MCRI), in collaboration with Liam Furst, Neuro-oncology group (MCRI), reNEW Melbourne.