Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress

Christophe Olivier (1, 2) , Lisa Oliver (1) , Lisenn Lalier (1, 3) , François M. Vallette (1, 3)

1 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
2 Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
3 LabCT - Laboratoire de Biologie des Cancers et de Théranostic [St Herblain, Nantes]

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 redoxmechanisms 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 highmetabolic 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.

Domaines: Cancer

Christophe Olivier, Lisa Oliver, Lisenn Lalier, François M. Vallette. Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress. Frontiers in Molecular Neuroscience, 2021. ⟨inserm-03136960⟩