RRC ID 68661
著者 Matsuda K, Sato A, Okada M, Shibuya K, Seino S, Suzuki K, Watanabe E, Narita Y, Shibui S, Kayama T, Kitanaka C.
タイトル Targeting JNK for therapeutic depletion of stem-like glioblastoma cells.
ジャーナル Sci Rep
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.
巻・号 2
ページ 516
公開日 2012-1-1
DOI 10.1038/srep00516
PII srep00516
PMID 22816039
PMC PMC3400080
MeSH Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology Brain Neoplasms / enzymology* Brain Neoplasms / mortality Brain Neoplasms / pathology Cell Differentiation / drug effects Cell Line, Tumor Glioblastoma / enzymology* Glioblastoma / mortality Glioblastoma / pathology Humans JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors* MAP Kinase Signaling System* / drug effects Male Mice Mice, Nude Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / enzymology* Phosphorylation / drug effects Protein Kinase Inhibitors / administration & dosage Protein Kinase Inhibitors / pharmacology Tumor Burden / drug effects Xenograft Model Antitumor Assays
IF 3.998
リソース情報
ヒト・動物細胞 T98G(RCB1954)