Injury programs shape glioblastoma

Glioblastoma is the most common and aggressive primary brain cancer in adults and is almost universally fatal due to its stark therapeutic resistance. During the past decade, although survival has not substantially improved, major advances have been made in our understanding of the underlying biology. It has become clear that these devastating tumors recapitulate features of neurodevelopmental hierarchies which are influenced by the microenvironment. Emerging evidence also highlights a prominent role for injury responses in steering cellular phenotypes and contributing to tumor heterogeneity. This review highlights how the interplay between injury and neurodevelopmental programs impacts on tumor growth, invasion, and treatment resistance, and discusses potential therapeutic considerations in view of these findings. Glioblastoma is a deadly brain cancer comprising cells that recapitulate normal neurodevelopmental lineage hierarchies.Increasing evidence suggests that injury responses superimpose onto these neurodevelopmental programs to fuel tumor heterogeneity and result from the growing tumor mass physically damaging the surrounding brain tissue, as well as from therapeutic intervention.Non-malignant cells within the normal brain tissue respond to tumor-induced injury by activating reactive programs, which in turn modulate glioblastoma biology.Tumor cells aberrantly mirror injury programs of their non-malignant counterparts by enacting latent reactive and regenerative responses.The interplay between neurodevelopmental and injury programs has therapeutic implications, and increased understanding of the molecular basis of these programs may lead to improved treatments.