Ion channel expression and function in glioblastoma multiforme (GBM): pathophysiological mechanisms and therapeutic potential

Glioblastoma Multiforme (GBM) is a highly malignant and diffusely invasive WHO Grade IV brain tumor arising from glial and neural stem cells. GBM is characterized by rapid proliferation and migration, aggressive invasion of local brain parenchyma, a hypoxic microenvironment, resistance to apoptosis and high vascular remodeling and angiogenesis. These hallmarks contribute to a near universal tumor recurrence after treatment or resection and poor patient prognosis. Ion channels, a superfamily of proteins responsible for permitting ion flux across otherwise impermeant membranes, show extensive remodeling in GBM with aberrant function mechanistically linked to manipulation of each of these hallmarks. In this review, we will discuss the known links between ion channel expression and activity and cellular processes that are enhanced or perturbed during GBM formation or progression. We will also discuss the extent to which basic or translational findings on ion channels in GBM samples or cell lines have shown preclinical promise towards the development of improved therapeutics against GBMs.