title: Targeting JNK for therapeutic depletion of stem-like glioblastoma cells.
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.
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
authors: Ken-ichiro
authors: K
authors: Matsuda
authors: Atsushi
authors: A
authors: Sato
authors: Masashi
authors: M
authors: Okada
authors: Keita
authors: K
authors: Shibuya
authors: Shizuka
authors: S
authors: Seino
authors: Kaori
authors: K
authors: Suzuki
authors: Eriko
authors: E
authors: Watanabe
authors: Yoshitaka
authors: Y
authors: Narita
authors: Soichiro
authors: S
authors: Shibui
authors: Takamasa
authors: T
authors: Kayama
authors: Chifumi
authors: C
authors: Kitanaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases