Inhibition of HSP90 as a Strategy to Radiosensitize Glioblastoma: Targeting the DNA Damage Response and Beyond.
HSP90 inhibition
HSP90i
NW457
glioblastoma
hypermigration
radiosensitization
radiotherapy
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
09
2020
accepted:
25
01
2021
entrez:
5
4
2021
pubmed:
6
4
2021
medline:
6
4
2021
Statut:
epublish
Résumé
Radiotherapy is an essential component of multi-modality treatment of glioblastoma (GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly activated DNA damage response (DDR) mechanisms as a consequence of oncogene overexpression, persistent replicative stress, and other so far unknown reasons. The molecular chaperone heat shock protein 90 (HSP90) plays an important role in the establishment and maintenance of treatment resistance, since it crucially assists the folding and stabilization of various DDR regulators. Accordingly, inhibition of HSP90 represents a multi-target strategy to interfere with DDR function and to sensitize cancer cells to radiotherapy. Using NW457, a pochoxime-based HSP90 inhibitor with favorable brain pharmacokinetic profile, we show here that HSP90 inhibition at low concentrations with
Identifiants
pubmed: 33816244
doi: 10.3389/fonc.2021.612354
pmc: PMC8011354
doi:
Types de publication
Journal Article
Langues
eng
Pagination
612354Informations de copyright
Copyright © 2021 Orth, Albrecht, Seidl, Kinzel, Unger, Hess, Kreutzer, Sun, Stegen, Nieto, Maas, Winssinger, Friedl, Walch, Belka, Zitzelsberger, Niyazi and Lauber.
Déclaration de conflit d'intérêts
All commercial rights on pochoximes (including epi-pochoxime F) were licensed by Nexgenic Pharmaceuticals (New York, NY, USA). NW consulted Nexgenic Pharmaceuticals, and received funding from Nexgenic Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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