A theory and a model to understand glioblastoma development both in the bulk and in the microinfiltrated brain parenchyma.

The prognosis of patients affected by glioblastoma remains dismal despite many efforts have been devoted worldwide in research and therapeutic strategies. Reasons of our failure include the fact that the patient harboring a glioblastoma always has two problems inside the brain, the bulk tumor and the parenchyma microinfiltrated; the other reason is that the tumor is able to grow dynamically adapting to the mutated conditions of its growth microenvironment. This paper tries to give an interpretation to the dynamic process of the tumor growth, from the beginning to the end of its natural history, dividing it in three phases, one pre-hypoxia and two post-hypoxia, and these are then correlated with the types of cancer stem cells (CSCs) involved. Furthermore, the paper proposes an original animal model to follow glioblastoma development in only one generation of mice, both in the bulk and in the brain parenchyma.