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Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo
Journal article   Open access   Peer reviewed

Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo

Renfei Du, Ahmed Y. Sanin, Wenjie Shi, Bing Huang, Ann-Christin Nickel, Andres Vargas-Toscano, Shuran Huo, Thomas Nickl-Jockschat, Claudia A. Dumitru, Wei Hu, …
Frontiers in pharmacology, Vol.15, 1468920
09/25/2024
DOI: 10.3389/fphar.2024.1468920
PMCID: PMC11461351
PMID: 39386028
url
https://doi.org/10.3389/fphar.2024.1468920View
Published (Version of record) Open Access

Abstract

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further.
 trihexyphenidyl glioblastoma mesenchymal transformation drug repurposing cystathionine beta-synthase

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