Nat Commun:华人学者共同参与!阻止多种癌细胞扩散,这种新药潜力无穷

2018-06-26 悠然 生物探索

抗癌就意味着要杀死癌细胞。事实是,在癌细胞扩散到全身之前,阻止癌细胞移动也非常重要。近日,科学家们带了好消息,他们发现冷冻并杀死癌细胞是有可能的。这一研究于6月22日发表在《Nature Communications》杂志上。

据论文的通讯作者、俄勒冈健康科学大学(OHSU)的Raymond Bergan教授介绍,当今大多数癌症治疗方法都是为了杀死癌症。但迄今为止,还没有人开发出一种可以阻止癌细胞在体内移动的疗法。

“绝大多数癌症如乳腺癌、前列腺癌、肺癌结肠癌等,如果在器官中仅是一个小肿块并且没有扩散,那么及早被发现的话,患者将会活下来;一般来说,如果发现晚了,肿块扩散到全身后,患者就会死去。” Bergan说,“昼夜不间断的细胞运动是关键。如果癌细胞扩散到全身后,尽管我们可以治疗它,但它仍会夺走你的生命。"

正因为此,几十年来,对癌细胞运动的研究一直是他的团队研究的重点。

阻止癌细胞移动

2011年,Bergan及其团队采取了一种新的研究方法——他们与化学家合作,共同发现了一种能抑制癌细胞移动的药物KBU2046。《Nature Communications》杂志曾发文概述了这个多学科小组对KBU2046的研究。KBU2046是一种化合物,研究人员发现它能在乳腺癌、前列腺癌、结肠癌和肺癌四种不同的实体癌人类细胞模型中抑制细胞运动。

Bergan说:“利用化学来探索生物学,我们发现了一种完美的药物,它只会抑制癌细胞的移动,而不会产生任何其他作用。”



Ryan Gordon, Ph.D., and Raymond Bergan, M.D., with members of their lab. Credit: OHSU/Kristyna Wentz-Graff.

提炼药物

“缩小特定药物化合物范围的过程是一个细化的过程”,Bergan指出:“我们从一种阻止细胞移动的化学物质开始,然后我们越来越精密地提炼这种化学物质,直到它完美地阻止了细胞,且没有副作用。由于所有的药物都有副作用,所以我们要尽可能寻找最具体的药物。最终我们发现,KBU2046能做到这一点。"

这种药物的关键在于接触热休克蛋白——细胞的“清洁剂( leaners)”。“其作用方式是,与这些更干净的蛋白质结合以阻止细胞运动,但对这些蛋白质没有其他影响。这是一个非同寻常的独特机制,我们花了很多年才弄清楚。”Bergan强调。

下一步,进行人体测试

这项研究的最终目的是寻找一种有益于人类的新疗法。论文作者之一Ryan Gordon说道:“我们正致力于开发一种新的治疗方法,以协助控制早期疾病,防止病人罹患无法治愈的晚期疾病。”目前,他们正在筹集资金进行IND (investigational new drug,试验性新药)研究。

此外,Bergan和另一通讯作者Karl Scheidt博士还成立了一家名为“第三海岸疗法”( Third Coast Therapeutics)的公司,旨在为患者提供这种疗法。

我们的最终目标是能够对患有乳腺癌的女性说:在我们这里,服用这种药片,你的癌症不会扩散到你的全身。前列腺癌、肺癌和结肠癌患者亦是如此。Bergan说,“迄今为止,这种药物在动物模型中对四种癌症类型(乳腺癌、结肠癌、肺癌、前列腺癌)有很好的疗效。我们的目标是让它造福于人类。"

多学科小组

值得一提的是,这项研究华人团队也有参与。调查组成员包括来自中国厦门大学、美国西北大学的化学家、芝加哥大学和华盛顿大学的研究人员。作者们认为,利用这个跨职能小组的优势是研究成功的关键。

Scheidt总结说:“我们已经掌握了大自然提供的线索,透过化学的力量,创造了一种全新的方法,潜在地控制了癌症的扩散。作为一个团队,我们能够共同努力并最终帮助癌症患者,这是一次真正有益的经历。”

原始出处:

Li Xu, Ryan Gordon, Rebecca Farmer, et al. Precision therapeutic targeting of human cancer cell motility. Nature Communications 9, 2454.

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    2019-02-25 liuli5079
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    2019-06-01 liye789132251
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    2018-06-28 yxch36
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