期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5632
关键词
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资金
- Miguel Servet Program
- FERO Foundation
- Bear Necessities Pediatric Cancer Foundation
- Fondazione Guido Berlucchi
- CNR/MIUR Epigenomic Flagship Project
- European Research Council [205819]
- Asociacion Espanola contra el Cancer
- Josef Steiner Cancer Research Foundation
- Cancer Research UK [A12077]
- NCI [R01 CA98018]
- European Research Council (ERC) [205819] Funding Source: European Research Council (ERC)
- ICREA Funding Source: Custom
- Cancer Research UK [12077, 13061] Funding Source: researchfish
Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.
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