| Autor: |
Morrent Thang, Clara Mellows, Lauren E. Kass, Sabrina Daglish, Emily M.J. Fennell, Breanna E. Mann, Alison R. Mercer-Smith, Alain Valdivia, Lee M. Graves, Shawn D. Hingtgen |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncology, Vol 32, Iss 3, Pp 200834- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2950-3299 |
| DOI: |
10.1016/j.omton.2024.200834 |
| Popis: |
Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) in vitro. We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
