Cancer Stem Cells: Significance in Origin, Pathogenesis and Treatment of Glioblastoma

Abstract

Cancer stem cells (CSCs), known also as tumor-initiating cells, are quiescent, pluripotent, self-renewing neoplastic cells that were first identified in hematologic tumors and soon after in solid malignancies. CSCs have attracted remarkable research interest due to their role in tumor resistance to chemotherapy and radiation treatment as well as recurrence. Extensive research has been devoted to the role of CSCs in glioblastoma multiforme (GBM), the most common primary brain tumor in adults, which is characterized by a dismal prognosis because of its aggressive course and poor response to treatment. The aim of the current paper is to provide an overview of current knowledge on the role of cancer stem cells in the pathogenesis and treatment resistance of glioblastoma. The six regulatory mechanisms of glioma stem cells (GSCs)—tumor microenvironment, niche concept, metabolism, immunity, genetics, and epigenetics—are reviewed. The molecular markers used to identify GSCs are described. The role of GSCs in the treatment resistance of glioblastoma is reviewed, along with future treatment options targeting GSCs. Stem cells of glioblastoma thus represent both a driving mechanism of major treatment difficulties and a possible target for more effective future approaches.

Cancer Stem Cells: What Do We Know about Them?

“…This article collection highlights the role of CSCs in the development and progression of malignant tumors. Thus, Biserova et al [ 5 ] have discussed how glioblastoma cells with stemness properties can contribute to tumor formation, growth and expansion. Stemness properties of glioblastoma cells can be regulated by a number of factors contributing to cell resistance to therapy and recurrence.…”

Integrative Analysis to Identify Genes Associated with Stemness and Immune Infiltration in Glioblastoma

“…Altered gene expression between stem cells and tumour cells have been attributed to differentially expressed and methylated promoter genes. DNA methylation status in specific promoters is responsible for immune surveillance [38]. There is a significant difference in epigenetic profiles within various grades of glioma as well.…”

Multimodal Role of PACAP in Glioblastoma

“…Subsequently, other investigators have detailed this correlation [35,36]. More specifically, hypoxia contributes to the creation of an environmental cue directly responsible for cancer stem cells (CSCs) maintenance [37][38][39][40]. The latter escape radiotherapy or chemotherapy are directly responsible for cell genesis, aggressiveness, self-renewal and multipotency leading to cancer recurrence [41,42].…”