又一用途:干细胞构建罕见癌症模型,快速筛选治疗药物
2016/08/04
近期,来自于约翰霍普金斯Kimmel癌症中心的研究团队表示,他们构建出干细胞癌症模型,能够用于快速筛选药物,将在罕见大脑疾病和癌症治疗中大显身手。


这篇于8月1日发表在《Clinical Cancer Research》期刊的最新学术文章,为治疗罕见性儿童脑瘤——成神经管细胞瘤找到治疗希望。

约翰•霍普金斯大学医学院助理教授、约翰霍普金斯Kimmel癌症中心成员Eric Raabe博士协同团队,以神经干细胞为模型构建出人类脑瘤细胞模型。相比于小鼠模型,这一成果将更有利于直接、快速筛选到真正适用于人类的治疗药物。

成神经管细胞瘤是一种多发于幼儿时期的恶性肿瘤。目前,对其标准治疗方案是手术治疗结合放化疗,70%—80%的成神经管细胞瘤患者通过常规治疗能够存活。但是,对于3型细胞瘤患者(28%)而言,已有的治疗药物并不能阻止病情复发,患者存活率仅为30%—40%。

如何有效治疗3型细胞瘤患者,以及其他罕见癌症?

近年来,科学家寻找新型或者优化治疗方案的一个策略是筛查常见癌细胞的基因数据库,与药物信息相匹配。然而,罕见癌症及其亚型并不在常见行列,而针对罕见肿瘤构建一个实验室培养细胞系非常困难。

Raabe团队提出一种新思路:他们以慢病毒为载体,将与3型成神经管细胞瘤相关的常见基因插入人类神经干细胞。随着干细胞的自我复制,癌症相关基因表达使得神经干细胞转变成癌细胞,这些癌细胞最终发展成肿瘤。

随后,研究人员从这一肿瘤组织中提取RNA样本,常见基因表达标签。这一标签可以与3大细胞系数据中的类似标签作比较。Raabe表示,他们希望这一由干细胞构建肿的瘤细胞模型能与现有的数据库相匹配。如果成功,他们将能够快速筛选到罕见癌症的潜在治疗药物。

事实上,他们成功了。借助这一系统,研究人员注意到细胞周期蛋白依赖性激酶抑制剂(CDK抑制剂),此类药物将有望治疗3型成神经管细胞瘤。

其中,一种CDK抑制剂药物palbociclib已获美国FDA批准,用于治疗晚期乳腺癌。Raabe团队发现,该药能够抑制50%以上的癌细胞生长。且相比于对照组,药物处理后的癌细胞死亡率高出3倍。

将3型成神经管细胞瘤植入小鼠体内使其患病,研究人员发现通过服用palbociclib药物,患病小鼠的寿命延长了近50%。目前,palbociclib等CDK抑制剂用于治疗多种儿童脑瘤的试验正处于临床Ⅰ期,

Raabe强调,虽然构建一个3型成神经管细胞瘤模型需要花费数年时间,但是这一依赖于干细胞的疾病模型可以用于筛选罕见癌症的有效治疗药物。

备注:本文参考自“Stem cells may speed up screening of drugs for rare cancers”。

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