Bibliographic Details
| Title: |
Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo |
| Authors: |
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, Siyu Duan, I. Erol Sandalcioglu, Roland S. Croner, Joshua Alcaniz, Wolfgang Walther, Carsten Berndt, Ulf D. Kahlert |
| Source: |
Frontiers in Pharmacology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
trihexyphenidyl, glioblastoma, mesenchymal transformation, drug repurposing, cystathionine beta-synthase, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fphar.2024.1468920/full; https://doaj.org/toc/1663-9812 |
| DOI: |
10.3389/fphar.2024.1468920 |
| Access URL: |
https://doaj.org/article/6f46caeb3c7e4375a3ce00e72c97f3d4 |
| Accession Number: |
edsdoj.6f46caeb3c7e4375a3ce00e72c97f3d4 |
| Database: |
Directory of Open Access Journals |
