Targeting Role of Glioma Stem Cells for Gliobastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is known to be the most common and lethal malignant primary brain tumor. Despite vigorous basic and clinical studies over the past decades, the prognosis of patients with GBM has remained dismal. The fundamental problem with these malignancies occurs due to tumor cells' highly infiltrative nature, precluding a complete surgical resection, and a productive or acquired resistance to cytotoxic therapy. Recent studies demonstrated that GBMs exhibited remarkable cellular heterogeneity and hierarchy containing self-renewing glioma stem cells (GSCs). The malignant growth of GBM can be propagated and sustained by GSCs that are endowed with highly efficient clonogenic and tumor initiation capacities. GSCs can be identified with technical support and are responsible for the invasive potential and recurrence of GBMs. They share core signaling pathways with normal neural stem cells, but also display critical distinctions that provide important clues for useful therapeutic targets. Therefore, targeting GSCs becomes priorities for the development of novel therapeutic paradigms. Herein, we reviewed the existing and promising targeting therapies for GSCs which could effectively inhibit the tumor invasion, proliferation and recurrence of GBMs. Significant features of GSCs, such as invasive growth pattern, angiogenic potential, resistance to traditional therapy and differentiation, are important therapeutic targets. More promising strategies should target GSCs themselves by taking advantages of highthroughput technologies and dissecting the intrinsic molecular nature of GSCs. Novel chemical medicines targeting these GSCs may represent one of the most important directions. Hopefully, this could shed a light on the path we are going to.

Induction of antigen-specific cytotoxic T-cell response by dendritic cells generated from ecto-mesenchymal stem cells infected with an adenovirus containing the MAGE-D4a gene

“…Over the years, researchers in basic and clinical studies have aimed to improve the survival rate for patients with GBM; however, the prognosis remains to be poor (19). Preclinical data and active immunotherapy studies have concentrated on synthetic antigen vaccination and tumor lysate strategies (20).…”

NOS2 expression in glioma cell lines and glioma primary cell cultures: correlation with neurosphere generation and SOX-2 expression

“…The ability to promote glioma relapse, angiogenesis, invasiveness and therapeutic resistance, renders GSCs a potential target for anti-glioblastoma therapy [10, 12–16]. Several studies suggest that gliomas are characterized by a markedly inflammatory environment and the inflammation seems to be involved in all steps of tumorigenesis promoting genomic instability, proliferation and survival of malignant cells, angiogenesis, resistance to therapy, local or systemic immunosuppression and also rising the metastatic process [17–20].…”

Combination Treatment with PPARγLigand and Its Specific Inhibitor GW9662 Downregulates BIS and 14-3-3 Gamma, Inhibiting Stem-Like Properties in Glioblastoma Cells

“…Glioblastoma stem cells (GSCs) are at the root of tumor recurrence and are regarded as a potential target for anticancer therapy [2, 3]. …”