Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Frontiers in Molecular Biosciences

Lisa Oliver¹  François M. Vallette³  Lisenn Lalier³  Christophe Olivier⁴ 

[1] CHU de Nantes, Nantes, France;Faculté des Sciences Pharmaceutiques et Biologiques, Nantes, France;LaBCT, ICO, Saint Herblain, France;Université de Nantes, INSERM, CRCINA, Nantes, France;

关键词: glioblastoma;    oxidative stress;    drug resistance;    tumor microenvironment;    nutrition;   

DOI  :  10.3389/fmolb.2020.620677

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown