Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Abstract

Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15–18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.

Effect of SFX-01 on proliferation of human glioblastoma cell lines

“…Spheroid formation has been proposed as a robust, independent predictor of glioma tumour progression 6 and the presence of glioma stem cells (GSCs), which are enriched in spheroids, may be connected to the drug resistance of GBM due to their enhanced antioxidant defence 7 and elevated DNA repair capacity. 8 In this report we firstly compared the growth inhibitory capacity of SFN from SFX-01 versus reference SFN using a series of tumour cell lines. Secondly we compared their effects against four low-passage GBM cell lines that had been generated and grown under physiological oxygen conditions.…”

Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: a mechanistic review

“…The first accepted surface marker for glioblastoma stem cells was CD133 [141] that it allows the subdivision of stem cells into two groups of CD133 + or cancer stem cells and CD133 − or non-cancer stem cells [142]. Other markers expressed in glioblastoma stem cells are CD15, CD184, CD44, A2B5, CD90, SOX2, OCT-4, SALL4, NANOG, ALDH1, L1CAM, KLF4, and so on [76,[143][144][145][146][147][148][149][150][151][152][153]. Some studies have reported that resveratrol is able to target glioma glioblastoma stem cells through various molecular pathways involved in self-renewal and several stem cell markers.…”

Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review)

“…However, long-term TMZ administration typically results in resistance, limiting its efficacy (15). The stem-like characteristics of GBM cells are primarily responsible for its resistance to chemotherapy, immunotherapy and radiation (16). Therefore, adjuvant therapy, such as chemotherapy or immunotherapy, may be applied to overcome drug resistance and to improve the survival rates of patients with GBM (17).…”