Brain Tumor Stem Cells as Therapeutic Targets in Models of Glioma

Abstract

At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells

“…Gliomas are heterogeneous tumors composed of a mixture of cells with differing phenotypes, including cancer stem cells [8,9]. Emerging models of glioma biology such as the stemness phenotype model [8] and the complex system model [9], support the concept that for a successful therapy, i.e., tumor elimination and prevention of relapse, all glioma cells should be the therapeutic target and should be completely eliminated. Consequently, it is essential to find drugs or a combination of drugs that have pankiller effects (defined as drugs that kill 100% of tumor cells) and that show relatively low toxicity to normal cells.…”

“…Chemotherapy is still a challenge, due to the inability to deliver effective concentrations of therapeutic agents into the central nervous system (CNS) across the blood brain barrier (BBB) [3][4][5], the toxicity to the surrounding normal brain tissue, the high systemic side effects and the resistant progression [6,7]. Gliomas are heterogeneous tumors composed of a mixture of cells with differing phenotypes, including cancer stem cells [8,9]. Emerging models of glioma biology such as the stemness phenotype model [8] and the complex system model [9], support the concept that for a successful therapy, i.e., tumor elimination and prevention of relapse, all glioma cells should be the therapeutic target and should be completely eliminated.…”

ALDH1 expression is correlated with pathologic grade and poor clinical outcome in patients with astrocytoma

“…11,12 As a critical target for glioma treatment, TSCs have stimulated wide interest. 14,15 Aldehyde dehydrogenase 1 (ALDH1) is a detoxifying enzyme that oxidizes intracellular aldehydes and thereby confers resistance to alkylating agents. It thus contributes to the oxidation of retinol to retinoic acid in early stem cell differentiation, and has been identified as a novel tumor stem-like cell marker in a variety of malignancies.…”

Aldehyde dehydrogenase 1 expression has prognostic significance in patients with glioma

“…In brain tumors, different types of stem cell markers may be used to identify CSCs, including CD133, Sox2, and CD44 (6,7), which are positively associated with pathological grade, and negatively associated with overall survival (OS) and progression-free survival (PFS) in patients with glioma (8,9).…”