日前,日本一个研究小组宣布,他们在动物实验中发现一种防止恶性胶质瘤复发的新方法,相关论文已经刊登在英国《科学报告》(Scientific Reports)杂志上。
恶性胶质瘤是一种非常难以治疗的恶性脑肿瘤,术后复发率较高。在日本,它是一种患者人数最多的恶性脑肿瘤,发病率为万分之一。能够重新制造癌细胞的“癌干细胞”被认为是导致恶性胶质瘤复发的原因。
日本山形大学和国立癌症研究中心的联合研究小组注意到,一种被称为JNK的蛋白激酶对于维持“癌干细胞”的存活必不可少,于是将美国制药公司为治疗帕金森氏症而开发的JNK抑制剂注射到脑内移植了恶性胶质瘤的实验鼠体内。结果发现,肿瘤中的“癌干细胞”减少到原有水平的十分之一以下。
如果向实验鼠脑内移植“癌干细胞”,再连续10天注射这种药物,也能够将“癌干细胞”减少到原有水平的十分之一以下甚至百分之一。药物对脑功能也没有影响。
研究小组负责人、山形大学教授北中千史说:“通过手术清除胶质瘤,再辅以这种药物,也许就能够阻止复发,让患者长期存活。”研究人员已经准备开展临床研究,有望5至7年后实现临床应用。(生物谷Bioon.com)
doi:10.1038/srep00516
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Targeting JNK for therapeutic depletion of stem-like glioblastoma cells
Ken-ichiro Matsuda; Atsushi Sato; Masashi Okada; Keita Shibuya; Shizuka Seino; Kaori Suzuki; Eriko Watanabe; Yoshitaka Narita; Soichiro Shibui; Takamasa Kayama; Chifumi Kitanaka
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