Progress in Glioma Stem Cell Research

Abstract

Glioblastoma multiforme (GBM) represents a diverse spectrum of primary tumors notorious for their resistance to established therapeutic modalities. Despite aggressive interventions like surgery, radiation, and chemotherapy, these tumors, due to factors such as the blood–brain barrier, tumor heterogeneity, glioma stem cells (GSCs), drug efflux pumps, and DNA damage repair mechanisms, persist beyond complete isolation, resulting in dismal outcomes for glioma patients. Presently, the standard initial approach comprises surgical excision followed by concurrent chemotherapy, where temozolomide (TMZ) serves as the foremost option in managing GBM patients. Subsequent adjuvant chemotherapy follows this regimen. Emerging therapeutic approaches encompass immunotherapy, including checkpoint inhibitors, and targeted treatments, such as bevacizumab, aiming to exploit vulnerabilities within GBM cells. Nevertheless, there exists a pressing imperative to devise innovative strategies for both diagnosing and treating GBM. This review emphasizes the current knowledge of GSC biology, molecular mechanisms, and associations with various signals and/or pathways, such as the epidermal growth factor receptor, PI3K/AKT/mTOR, HGFR/c-MET, NF-κB, Wnt, Notch, and STAT3 pathways. Metabolic reprogramming in GSCs has also been reported with the prominent activation of the glycolytic pathway, comprising aldehyde dehydrogenase family genes. We also discuss potential therapeutic approaches to GSC targets and currently used inhibitors, as well as their mode of action on GSC targets.

Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review

“…However, challenges abound in the clinical application of HIF-related therapies. The lack of standardization in research methodologies impedes quantitative meta-analysis, while genetic mutations in GBM and therapy effects outside target sites present additional hurdles [ 13 , 144 , 145 ]. The complex and dynamic nature of the hypoxic tumor microenvironment may limit the efficacy of single-target HIF therapies, potentially leading to therapy resistance.…”

Prospects of marine-derived compounds as potential therapeutic agents for glioma

“…PIP3 activation reduces AKT activation while increasing the expression of mTOR complexes 1 and 2 (Ramar et al. 2023 ). Activation of mTORC1 increases cellular development by enhancing the anabolic process of other macromolecule formation while decreasing the catabolic response.…”

Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy

“…Activation of Notch signaling in GBM promotes cell proliferation and boosts survival capabilities [15]. In certain situations, the initiation of Notch signaling may lead to the differentiation of tumor stem cells, giving rise to various cell types [16], potentially influencing tumor heterogeneity and treatment resistance [17]. Simultaneously, Notch signaling activation may impact surrounding cells, angiogenesis, and immune responses, thereby influencing tumor growth and dissemination [18].…”