Epichaperome Inhibition by PU-H71-Mediated Targeting of HSP90 Sensitizes Glioblastoma Cells to Alkylator-Induced DNA Damage.

ABSTRACT:

Background

Targeted therapies have been largely ineffective against glioblastoma (GBM) owing to the tumor's heterogeneity and intrinsic and adaptive treatment resistance. Targeting multiple pro-survival pathways simultaneously may overcome these limitations and yield effective treatments. Heat shock protein 90 (HSP90), an essential component of the epichaperome complex, is critical for the proper folding and activation of several pro-survival oncogenic proteins that drive GBM biology.

Methods

Using a panel of biochemical and biological assays, we assessed the expression of HSP90 and its downstream targets and the effects of PU-H71, a highly specific and potent HSP90 inhibitor, on target modulation, downstream biochemical alterations, cell cycle progression, proliferation, mi

SUBMITTER: Sharma P 

PROVIDER: S-EPMC11640441 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature