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The adaptive transition of glioblastoma stem cells and its implications on treatments
Zeyu Wang1, Hao Zhang1, Shengchao Xu1
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P.R. China.
Abstract:
Glioblastoma is the most malignant tumor occurring in the human central nervous system with overall median survival time <14.6 months. Current treatments such as chemotherapy and radiotherapy cannot reach an optimal remission since tumor resistance to therapy remains a challenge. Glioblastoma stem cells are considered to be responsible for tumor resistance in treating glioblastoma. Previous studies reported two subtypes, proneural and mesenchymal, of glioblastoma stem cells manifesting different sensitivity to radiotherapy or chemotherapy. Mesenchymal glioblastoma stem cells, as well as tumor cells generate from which, showed resistance to radiochemotherapies. Besides, two metabolic patterns, glutamine or glucose dependent, of mesenchymal glioblastoma stem cells also manifested different sensitivity to radiochemotherapies. Glutamine dependent mesenchymal glioblastoma stem cells are more sensitive to radiotherapy than glucose-dependent ones. Therefore, the transition between proneural and mesenchymal subtypes, or between glutamine-dependent and glucose-dependent, might lead to tumor resistance to radiochemotherapies. Moreover, neural stem cells were also hypothesized to participate in glioblastoma stem cells mediated tumor resistance to radiochemotherapies. In this review, we summarized the basic characteristics, adaptive transition and implications of glioblastoma stem cells in glioblastoma therapy.
Insights
Glioblastoma stem cells drive tumor resistance. Subtype transitions and metabolic shifts, like glutamine dependence, impact glioblastoma treatment sensitivity, affecting patient survival.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
- Tumor Microenvironment
Background:
- Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis.
- Current therapies (chemotherapy, radiotherapy) face challenges due to tumor resistance.
- Glioblastoma stem cells (GSCs) are implicated in therapeutic resistance.
Purpose of the Study:
- To review the characteristics and adaptive transitions of GSCs.
- To explore the role of GSCs in glioblastoma therapy resistance.
- To understand metabolic and subtype influences on treatment sensitivity.
Main Methods:
- Literature review of GSC subtypes (proneural, mesenchymal).
- Analysis of metabolic dependencies (glutamine, glucose) in GSCs.
- Examination of GSC transitions and their impact on therapy.
Main Results:
- Mesenchymal GSCs and their derived cells exhibit resistance to radiochemotherapy.
- Metabolic state influences GSC sensitivity: glutamine-dependent GSCs are more sensitive than glucose-dependent ones.
- Plasticity between GSC subtypes and metabolic states may drive therapy resistance.
Conclusions:
- Glioblastoma stem cell plasticity is a key factor in treatment failure.
- Targeting GSC subtypes and metabolic pathways offers potential therapeutic strategies.
- Understanding GSC behavior is crucial for improving glioblastoma treatment outcomes.
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