Abstract
Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly resistant to chemo and radiotherapy. These cells are believed to be responsible for tumor relapses and patients' fatal outcome after developing a recurrent Glioblastoma (GBM) or High Grade Glioma (HGG). GSCs are cells under replicative stress with high demands on NAD+ supply to repair DNA, maintain self-renewal capacity and to induce tumor plasticity. NAD+ feeds Poly-ADP polymerases (PARP) and NAD+-dependent deacetylases (SIRTUINS) contributing to GSC phenotype. This energetic core axis is mainly controlled by the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT), an important oncogene contributing to tumor dedifferentiation. Targeting GSCs depicts a new frontier in Glioma therapy; hence NAMPT could represent a key regulator for GSCs maintenance. Its inhibition may attenuate GSCs properties by decreasing NAD+ supply, consequently contributing to a better outcome together with current therapies for Glioma control.
Highlights
Gliomas are the most prevalent primary brain cancer in adults
Ablation of nicotinamide phosphoribosyltransferase (NAMPT) showed to impair Schwann cell differentiation program associated to reduced NAD+ levels, counteracting the phenotype found in tumor cells but reinforcing the idea that an adequate NAD+ level is required for a fine tuned balance on cell-fate definition toward differentiation programs [108]
This energetic core axis is mainly controlled by the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT), an important oncogene contributing to tumor dedifferentiation
Summary
Gliomas are the most prevalent primary brain cancer in adults. Arising from glia cells, Gliomas involve a broad category of tumors including astrocytoma, oligodendroglioma, and glioblastoma (GBM). Regardless of tumor aggressiveness, malignancy and infiltration, these glia-derived tumors rarely exceed a median survival time of 12–14 months [1, 2]. Driven by the infiltrative nature of these tumors, the clinical approach is difficult and relapses often occur with fatal consequences. There are many physiological barriers to the development of successful treatments. Blood-brain barrier (BBB) is a major limitation when it comes to deliver a chemotherapy-based treatment. Surgical resection is an ineffective long-term procedure since Gliomas infiltrate together with healthy brain tissue and their resection become virtually impossible. Gliomas relapse in highly radio- and chemo-resistant forms
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