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GIOVANNI GRASSO

When Neuroprotection Becomes a Potential Ally of High-Grade Glioma

Abstract

Despite the use of multimodal treatment regimens, high-grade gliomas (HHGs) are tumors invariably associated with a poor prognosis. The median patient survival after diagnosis is approximately 1 year, through surgery/radiation and chemotherapy treatments.To date, traditional approaches fail to treat efficiently HHGs because surgery does not completely remove the tumor without damaging the brain, radiation therapy cannot be used beyond a certain threshold dose, and chemotherapy has shown limited efficacy and toxic effects. Notwithstanding many attempts at improving outcome using novel agents, the treatment of this disease has not improved in more than a decade. Although scientific and technological advances are driving the continuous development and refinement of surgical tools and methods, with the goal of increasing the clinical benefit of tumor resection, HGGs exemplify the uncommon scenario where there is always significant residual disease after surgery. It is also well known that the brain represents an immune-privileged site, where immune-mediated removal of microscopic disease is limited, leaving a large number of cells that can only be ablated by chemo-radiotherapy. Mechanisms of treatment resistance are still poorly understood, but a pool of cells with stem-like features associated with upregulated DNA repair mechanisms and a highly migratory phenotype are thought to represent a resistant population that survive and repopulate the tumor after cytotoxic treatments.