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Targeting JNK for therapeutic depletion of stem-like glioblastoma cells.
- Source :
-
Scientific reports [Sci Rep] 2012; Vol. 2, pp. 516. Date of Electronic Publication: 2012 Jul 19. - Publication Year :
- 2012
-
Abstract
- Control of the stem-like tumour cell population is considered key to realizing the long-term survival of patients with glioblastoma, one of the most devastating human malignancies. To date, possible therapeutic targets and targeting methods have been described, but none has yet proven to target stem-like glioblastoma cells in the brain to the extent necessary to provide a survival benefit. Here we show that targeting JNK in vivo, the activity of which is required for the maintenance of stem-like glioblastoma cells, via transient, systemic administration of a small-molecule JNK inhibitor depletes the self-renewing and tumour-initiating populations within established tumours, inhibits tumour formation by stem-like glioblastoma cells in the brain, and provide substantial survival benefit without evidence of adverse events. Our findings not only implicate JNK in the maintenance of stem-like glioblastoma cells but also demonstrate that JNK is a viable, clinically relevant therapeutic target in the control of stem-like glioblastoma cells.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents pharmacology
Brain Neoplasms mortality
Brain Neoplasms pathology
Cell Differentiation drug effects
Cell Line, Tumor
Glioblastoma mortality
Glioblastoma pathology
Humans
Male
Mice
Mice, Nude
Neoplastic Stem Cells drug effects
Phosphorylation drug effects
Protein Kinase Inhibitors administration & dosage
Protein Kinase Inhibitors pharmacology
Tumor Burden drug effects
Xenograft Model Antitumor Assays
Brain Neoplasms enzymology
Glioblastoma enzymology
JNK Mitogen-Activated Protein Kinases antagonists & inhibitors
MAP Kinase Signaling System drug effects
Neoplastic Stem Cells enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 22816039
- Full Text :
- https://doi.org/10.1038/srep00516