美国研制出能迫使癌细胞自我毁灭的抗癌药物

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本帖最后由小P 于 2013-11-10 19:25 编辑

药物联合治疗使癌细胞自相残杀

美国《每日科学》网站文章称：一项临床前试验的结果显示，在弗吉尼亚州立大学梅西癌症中心进行的一种新的药物联合治疗，能够杀死结肠、肝脏、肺、肾脏、乳腺和脑部的癌细胞，而对非癌细胞几乎没有影响。这些结果为那些计划进行一个 “未来的阶段I临床试验”——检测这种疗法在一个小的患者群体中的安全性——的研究者们奠定了基础。

这项研究试图确定是否多重激酶抑制剂索拉非尼（Sorafenib）/瑞乏非尼（regorafenib），与临床上相关的磷脂酰肌醇3激酶（PI3K）-胸腺瘤病毒原癌基因（AKT）抑制剂联合杀死肿瘤细胞。

“估计临床试验何时开放以进一步验证这种药物联合治疗，还为时过早，但是我们目前正在计划阶段，也被这些实验室实验结果鼓舞着，”VCU梅西癌症中心的发展疗法研究项目成员、VCU医学院的血液学、肿瘤学和姑息治疗部门的助理教授、医学博士和肿瘤学家Andrew Poklepovic称。

“我们也受到一个事实的鼓舞，那就是在这种疗法中使用的药物，已经被FDA批准用来治疗某种癌症或者当前正在其它临床试验研究中。”

这项研究由Paul Dent博士带领，发表在11月份的Molecular Pharmacology上，表明药物索拉非尼和瑞乏非尼与一大类PI3K/AKT抑制剂的药物联合在一起，杀死了各种各样的癌症细胞。索拉非尼和瑞乏非尼通过阻止称为激酶的这种酶的产生而发挥作用，这种酶对癌细胞的生长和生存都非常重要。当前，索拉非尼已经被FDA批准用来治疗肾脏癌和肝癌，瑞乏非尼当前被批准用来治疗结肠直肠癌。然而，索拉非尼和瑞乏非尼不直接影响PI3K和AKT激酶，它们在促进癌细胞生存中也非常活跃。一种PI3K/AKT抑制剂添加到索拉非尼和瑞乏非尼组合后，戏剧性地增加了细胞死亡，甚至有效地对抗了使一种或其它药物不太有效、具有某种突变的细胞。

“我们知道，有一定的细胞过程在癌症中是经常失调的，它对细胞增殖和生存都很重要，但是如果你关闭其中一个，细胞通过依赖另外一个，通常可以补偿。”癌细胞信号环球公司的特聘教授、VCU梅西癌症中心的发展疗法研究项目成员、同时也是VCU医学院神经外科系的副主席Dent称，“我们正在阻止几个这样的生存通道，癌细胞为了生存，好不夸张的说，它们正在消化它们自己。”

这项研究成果表明，联合疗法通过物理相互作用分子来阻止生存通路，诱导一个称为自我吞噬的毒性作用。自我吞噬是一个防护过程，在此过程中，当细胞缺乏了生存必需的资源时，它们代谢它们自己。

“许多团队都在尝试抑制两个生存信号通路的方法，但是我们的方法能更显著阻止这些通道，因此使其更具有先进性，”Dent说。“基于在多种癌症类型中发现的很广范围的效果，我们的这项发现应该会为很多不同的癌症患者带来益处。”

小P · 发表于 2013-11-10 19:22:12

本帖最后由小P 于 2013-11-10 19:25 编辑

原文及网址:

http://www.sciencedaily.com/releases/2013/11/131105103631.htm

Drug Combination Therapy Causes Cancer Cells to 'Eat Themselves'

Nov. 5, 2013 — Results from a recent preclinical study have shown that a new drug combination therapy being developed at Virginia Commonwealth University Massey Cancer Center effectively killed colon, liver, lung, kidney, breast and brain cancer cells while having little effect on noncancerous cells. The results lay the foundation for researchers to plan a future phase 1 clinical trial to test the safety of the therapy in a small group of patients.

"It is still too premature to estimate when a clinical trial will open to further test this drug combination therapy, but we are now in the planning phase and encouraged by the results of these laboratory experiments," says Andrew Poklepovic, M.D., oncologist and member of the Developmental Therapeutics research program at VCU Massey Cancer Center and assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine. "We are also encouraged by the fact that the drugs used in this therapy are either already approved by the FDA to treat certain cancers or are currently being investigated in other clinical trials."

Featured in the journal Molecular Pharmacology, the study led by Paul Dent, Ph.D., demonstrated that the drugs sorafenib and regorafenib synergize with a class of drugs known as PI3K/AKT inhibitors to kill a variety of cancers. Sorafenib and regorafenib work by blocking the production of enzymes called kinases, which are vital to the growth and survival of cancer cells. Sorafenib is currently approved by the FDA to treat kidney and liver cancers, and regorafenib is currently approved for the treatment of colorectal cancer. However, sorafenib and regorafenib do not directly affect PI3K and AKT kinases, which are also very active in promoting cancer cell survival. The addition of a PI3K/AKT inhibitor to the combination of sorafenib and regorafenib dramatically increased cell death and was even effective against cells with certain mutations that make one or the other drug less effective.

"We know that there are certain cellular processes that are frequently dysregulated in cancers and important to cell proliferation and survival, but if you shut down one, then cells can often compensate by relying on another," says Dent, Universal Corporation Distinguished Professor for Cancer Cell Signaling and member of the Developmental Therapeutics research program at VCU Massey Cancer Center as well as vice chair of the Department of Neurosurgery at VCU School of Medicine. "We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive."

Results of the study showed that the combination therapy killed the cells by physically interacting with molecules to block the survival pathways and induce a toxic effect known as autophagy. Autophagy is a protective process where cells metabolize themselves when starved of the resources needed to survive.

"Many groups are trying the approach of inhibiting two survival signaling pathways, but our approach takes this further by blocking significantly more of these pathways," says Dent. "Our findings could benefit many different cancer patients based on the broad range of effects seen in multiple cancer types."