Diffuse Low-Grade Glioma Associated Stem Cells

Precision medicine is a medical model that proposes the customization of healthcare, with medical decisions, practices, and/or products being tailored to the individual patient, taking advantage of a multimodal approach considering not only patient’s genetic content but also other molecular and cellular analysis. Because of their heterogeneous clinical behavior, low-grade glioma (LGG) can benefit from this approach. At this regard, recent publications took advantage of integrated wide-genome studies to identify genetic signatures endowed with a prognostic potential. However, there is evidence that cancer progression is driven not only by genetic alterations but also by the tumor microenvironment. To deepen the comprehension of the role played by this latter on LGG heterogeneity, we isolated from glioma a population of stem cells, named Glioma-Associated Stem Cell (GASC), representative of the tumor microenvironment. Importantly, GASC resulted to be the strongest predictors of LGG patients’ overall survival and malignant progression free survival, outperforming the state-of-the-art prognostic factors, including IDH1/2 mutation and 1p/19q co-deletion. In this chapter, we will first briefly review the increasing knowledge on the role played by the tumor microenvironment. Subsequently, we will focus our attention on GASC and their ability to increase the biological aggressiveness of glioma stem cells through the release of extracellular vesicles named exosomes. Finally we will demonstrate how this patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies aimed at targeting the tumor stroma.