Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo
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 w...
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Frontiers Media S.A.,
2024-09-01T00:00:00Z.
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| 100 | 1 | 0 | |a Renfei Du |e author |
| 700 | 1 | 0 | |a Renfei Du |e author |
| 700 | 1 | 0 | |a Ahmed Y. Sanin |e author |
| 700 | 1 | 0 | |a Wenjie Shi |e author |
| 700 | 1 | 0 | |a Bing Huang |e author |
| 700 | 1 | 0 | |a Bing Huang |e author |
| 700 | 1 | 0 | |a Ann-Christin Nickel |e author |
| 700 | 1 | 0 | |a Andres Vargas-Toscano |e author |
| 700 | 1 | 0 | |a Shuran Huo |e author |
| 700 | 1 | 0 | |a Thomas Nickl-Jockschat |e author |
| 700 | 1 | 0 | |a Claudia A. Dumitru |e author |
| 700 | 1 | 0 | |a Wei Hu |e author |
| 700 | 1 | 0 | |a Siyu Duan |e author |
| 700 | 1 | 0 | |a I. Erol Sandalcioglu |e author |
| 700 | 1 | 0 | |a Roland S. Croner |e author |
| 700 | 1 | 0 | |a Joshua Alcaniz |e author |
| 700 | 1 | 0 | |a Wolfgang Walther |e author |
| 700 | 1 | 0 | |a Carsten Berndt |e author |
| 700 | 1 | 0 | |a Ulf D. Kahlert |e author |
| 245 | 0 | 0 | |a Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo |
| 260 | |b Frontiers Media S.A., |c 2024-09-01T00:00:00Z. | ||
| 500 | |a 1663-9812 | ||
| 500 | |a 10.3389/fphar.2024.1468920 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a trihexyphenidyl | ||
| 690 | |a glioblastoma | ||
| 690 | |a mesenchymal transformation | ||
| 690 | |a drug repurposing | ||
| 690 | |a cystathionine beta-synthase | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Frontiers in Pharmacology, Vol 15 (2024) | |
| 787 | 0 | |n https://www.frontiersin.org/articles/10.3389/fphar.2024.1468920/full | |
| 787 | 0 | |n https://doaj.org/toc/1663-9812 | |
| 856 | 4 | 1 | |u https://doaj.org/article/6f46caeb3c7e4375a3ce00e72c97f3d4 |z Connect to this object online. |