In vitro models of brain cancer

Glioblastoma multiforme (GBM) is the most common primary brain malignancy in adults. Despite continuing advances in surgical treatment and combined chemoradiotherapy, little improvement in overall median survival has been seen. Therapeutic advances in neuro-oncology are likely to arise through the systematic dissection of the fascinating tumor biology that exists in GBM. If we are to tackle questions such as What is the cell of origin in brain cancer? and How do these cells evade standard treatment methods and ultimately identify the Achilles' heel of this aggressive disease? a scientific prerequisite is the availability of a robust and reliable in vitro model of glioma. What follows in this chapter is a discussion of the current state of knowledge in the generation of in vitro models of glioblastoma. Past and current models will be considered with their advantages and shortcomings highlighted. We will discuss the principles of in vitro cytotoxic assays and how translatable therapies emerge from this approach. We discuss the cell of mutation and cell of origin in GBM and how modeling oncogenic transformation can shed new light on this controversial topic. This chapter, we hope, will function as a timeline in the evolution of in vitro models of brain cancer. It illustrates how far we have come in our understanding of brain cancer but additionally highlights the barriers we face and must overcome to ensure that a cure remains within sight.