期刊
ONCOTARGET
卷 8, 期 15, 页码 24753-24761出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15800
关键词
pediatric glioblastoma; acid ceramidase inhibitors; carmofur; glioblastoma; medulloblastoma
资金
- Musella Foundation
- Department of Neurosurgery Larson Endowment Grant
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4.6-50 mu M). This data suggests acid ceramidase as a novel drug target for adjuvant pediatric brain tumor therapies. Of these acid ceramidase inhibitors, carmofur has seen clinical use in Japan since 1981 for colorectal cancers and is a promising drug to undergo further animal studies and subsequently a clinical trial as a treatment for pediatric patients with brain tumors.
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