Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme.
Fiche publication
Date publication
juillet 2024
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NOEL Georges, Dr BURCKEL Hélène
Tous les auteurs :
Bou-Gharios J, Noël G, Burckel H
Lien Pubmed
Résumé
Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. The standard clinical treatment of GBM includes a maximal surgical resection followed by concomitant radiotherapy (RT) and chemotherapy sessions with Temozolomide (TMZ) in addition to adjuvant TMZ cycles. Despite the severity of this protocol, GBM is highly resistant and recurs in almost all cases while the protocol remains unchanged since 2005. Limited-diffusion or chronic hypoxia has been identified as one of the major key players driving this aggressive phenotype. The presence of hypoxia within the tumor bulk contributes to the activation of hypoxia signaling pathway mediated by the hypoxia-inducing factors (HIFs), which in turn activate biological mechanisms to ensure the adaptation and survival of GBM under limited oxygen and nutrient supply. Activated downstream pathways are involved in maintaining stem cell-like phenotype, inducing mesenchymal shift, invasion, and migration, altering the cellular and oxygen metabolism, and increasing angiogenesis, autophagy, and immunosuppression. Therefore, in this review will discuss the recent preclinical and clinical approaches that aim at targeting tumor hypoxia to enhance the response of GBM to conventional therapies along with their results and limitations upon clinical translation.
Mots clés
Humans, Glioblastoma, metabolism, Brain Neoplasms, pathology, Animals, Cell Hypoxia, Tumor Hypoxia, Signal Transduction
Référence
Cell Death Dis. 2024 07 13;15(7):503