AUTHOR=Du Renfei , Sanin Ahmed Y. , Shi Wenjie , Huang Bing , Nickel Ann-Christin , Vargas-Toscano Andres , Huo Shuran , Nickl-Jockschat Thomas , Dumitru Claudia A. , Hu Wei , Duan Siyu , Sandalcioglu I. Erol , Croner Roland S. , Alcaniz Joshua , Walther Wolfgang , Berndt Carsten , Kahlert Ulf D. TITLE=Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1468920 DOI=10.3389/fphar.2024.1468920 ISSN=1663-9812 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.