Abstract

Glioblastoma multiforme (GBM) is an incurable cancer with a rapid progression and a prognosis of month from the time of diagnosis. Given the resistance to all known therapies, new paradigms to understand this disease and identify novel therapeutic targets are sorely needed. We have used genetically engineered models to ablate GBM relevant tumour suppressors in brain cells. Our fully penetrant mouse models indicate that adult stem cells and progenitors are preferential sites of tumour initiation. As such, further study of these cells, and how they transform may provide unique insights into tumour development and progression. Our efforts to understand whether additional cell types can give rise to GBM indicate that fully differentiated brain cells are considerably more resistant to tumour suppressor mediated transformation than are stem cells, but in contrast, OPC progenitor cells are also able to give rise to GBM that, while pathologically similar to stem cell derived tumours, also have unique growth and molecular properties that distinguish them clearly. I will discuss the state of understanding of these tumours and the implications for cancer stem cells and therapeutic opportunities.