Abstract
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.
Original language | English |
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Pages (from-to) | 326-333 |
Number of pages | 8 |
Journal | Journal of Molecular Neuroscience |
Volume | 59 |
Issue number | 3 |
DOIs | |
Publication status | Published - 27 Nov 2015 |
Keywords
- Antineoplastic Agents/pharmacology
- Azepines/pharmacology
- Benzamides/pharmacology
- Brain Neoplasms/metabolism
- Brain-Derived Neurotrophic Factor/pharmacology
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Humans
- Medulloblastoma/metabolism
- Membrane Glycoproteins/antagonists & inhibitors
- Protein Kinase Inhibitors/pharmacology
- Protein-Tyrosine Kinases/antagonists & inhibitors
- Receptor, trkB
- Signal Transduction