Project 458947

Medulloblastoma is the most common cancerous brain tumour in children-one out of five childhood brain tumours are medulloblastoma. While the majority of ill health and death occurs due to metastasis, most research focuses on the initial or primary tumour. Metastases are found almost exclusively on thin membranes (called leptomeninges) that surround the brain and spinal cord; the cancer can spread through the blood and the fluid around the brain and spine. Unfortunately, very little is known about this microenvironment and there are currently no drugs for the treatment of this disease. A cancer cell is, by definition, genetically unstable and bestows the tumour cell with near-infinite ability to change in an ideal environment. The microenvironment is the most important source of selective pressure, sculpting the tumour's ability to spread and multiply. The brain is wholly unlike any other site of tumour growth in the body and, as such, asserts profound selective pressure on cancer cells. The purpose of my project is to understand how the leptomeningeal microenvironment is colonized and what promotes the attachment and homing of metastases to this location. I hypothesize that the leptomeningeal cells are secreting factors that support the survival of metastatic cells and that some cells within the primary tumour have differing capacities for growth and metastasis. To test this, I will conduct an analysis to determine what is secreted and employ single-cell protein profiling to examine differences between primary and metastatic cells using metastatic medulloblastoma models. I will then validate my findings using gene sequencing on patient tumour samples to pinpoint genes or proteins of interest. Lastly, I will look for FDA-approved drugs that specifically target cancer cells without harming normal cells in the central nervous system. I believe findings from my project will present an opportunity to improve treatment options for this highly burdened population.