Modelling how the brain microenvironment influences therapy response and metastasis of the most common childhood brain tumour

Medulloblastoma is the most common type of malignant paediatric brain tumour, accounting for 10% of cancer deaths in children. While survival rates have improved in recent years, metastatic spread is almost universally fatal. Current therapies also cause irreparable damage to the surrounding brain leading to decreased quality of life in surviving patients, consequently there is a need for new targeted therapy options. The degree of metastatic spread and resistance to current therapies is influenced by the underlying molecular subtype of the tumour. Development of novel therapies therefore requires reliable models which reflect subgroup specific behaviour (resistance and migration capability).
Medulloblastoma research has traditionally relied on either basic two-dimensional (2D) culture or orthotopic mouse models, neither of which accurately recapitulates a child's brain. We have recently developed a 3D tumour microenvironment model (Linke et al 2020), which recapitulates resistance and migration patterns observed in patients. In addition to being more representative, these studies take a fraction of the time and are far cheaper than animal-intensive projects.
Our in depth molecular (single cell analyses) and metabolic (3D OrbiSIMs) analyses (Linke et al in preparation) have given us further insights into how medulloblastoma cells interact with their microenvironment within these models. The student will therefore use these findings to further tailor our model, making it even more relevant to patients.
The overall aim being to gain an in-depth understanding of how the tumour interacts with surrounding normal cells and tissue to produce a microenvironment that is conducive to tumour cell migration and resistance. These findings will help to guide future clinical trials in children with medulloblastoma and have the potential to support studies of other paediatric brain tumours.