Overcoming therapeutic resistance in glioblastoma: Moving beyond the sole targeting of the glioma cells

Abstract Glioblastoma remains one of the most fatal cancers in humans. Despite the advent of optimal surgical resection, guided radiotherapy, and the addition of chemotherapy (temozolomide; TMZ) average survival remains at a dismal 14.6 months with very few long-term survivors. In this chapter we will discuss the various mouse and human glioma model systems that are used and the generation of in vivo selected models that recapitulate TMZ resistance together with the promise of repurposing disulfiram in the setting of relapsed glioblastoma. In addition, we will move beyond the sole targeting of the glioma cells and discuss the impact of the tumor microenvironment both at the level of the normal cellular repertoire that includes resident and recruited immune cells and the molecular and biophysical properties that contribute to gliomagenesis and therapeutic resistance where exciting new and novel therapeutic options are emerging.