期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2020.620677
关键词
glioblastoma; oxidative stress; drug resistance; tumor microenvironment; nutrition
资金
- INSERM/University of Nantes
GBM is a common primary brain tumor with poor prognosis, driven by GSCs in specialized microenvironments and characterized by resistance to therapy. ROS play a dual role in controlling cellular stability, affecting cell cycle, progression, and drug resistance in GBM, while also inducing cell death programs like apoptosis and autophagy. The metabolic adaptation and stromal components in the microenvironment contribute to oxidative stress and drug resistance in GBM progression.
Glioblastomas (GBM) are the most common primary brain tumor with a median survival of 15 months. A population of cells with stem cell properties (glioblastoma stem cells, GSCs) drives the initiation and progression of GBM and is localized in specialized microenvironments which support their behavior. GBM are characterized as extremely resistant to therapy, resulting in tumor recurrence. Reactive oxygen species (ROS) control the cellular stability by influencing different signaling pathways. Normally, redox systems prevent cell oxidative damage; however, in gliomagenesis, the cellular redox mechanisms are highly impaired. Herein we review the dual nature of the redox status in drug resistance. ROS generation in tumor cells affects the cell cycle and is involved in tumor progression and drug resistance in GBM. However, excess ROS production has been found to induce cell death programs such as apoptosis and autophagy. Since GBM cells have a high metabolic rate and produce high levels of ROS, metabolic adaptation in these cells plays an essential role in resistance to oxidative stress-induced cell death. Finally, the microenvironment with the stromal components participates in the enhancement of the oxidative stress to promote tumor progression and drug resistance.
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