OTS964我们草根的福音来了！

真的多了份希望！

癌症路上不孤独，挺到最后总是有好消息，加油

谢谢楼主！！

转自丁香园
Highly Effective New Anti-Cancer Drug Shows Few Side Effects in Mice
在小鼠体内显示出高度有效的抗癌新药并少有副作用
A new drug, known as OTS964, can eradicate aggressive human lung cancers transplanted into mice, according to a report in Science Translational Medicine. The drug, given as a pill or by injection, inhibits the action of a protein that is overproduced by several tumor types, including lung and breast, but is rarely expressed in healthy adult tissues. Without this protein, cancer cells fail to complete the cell-division process and die.
《科学转化医学》的一份报告显示，一种被称为OTS964的新药能够彻底根除移植到小鼠体内的人类恶性肺癌。这种药物被制成丸剂或者注射剂，它能够抑制一种在多种肿瘤（包括肺癌与乳腺癌）组织中过度表达而在正常成年人组织中极少表达的蛋白质的活性。如果没有这种蛋白质，癌症细胞则无法完成细胞分裂并死亡。
When taken by mouth, the drug was well tolerated with limited toxicity. An intravenous form, delivered within a liposome, was just as effective with fewer side effects. Both approaches—described in the October 22, 2014 issue of STM—led to complete regression of transplanted tumors.
通过口服给药，这种药物毒性有限因此耐受性很好。通过脂质体静脉给药，药效显著并且副作用很小。这两种给药方式——2014年10月22日发表在《科学转化医学》上——都能使移植的肿瘤组织衰亡。
“We identified the molecular target for this drug ten years ago, but it took us nearly a decade to find an effective way to inhibit it,” said study author Yusuke Nakamura, MD, PhD, professor of medicine at the University of Chicago and deputy director of the University’s Center for Personalized Therapeutics. “We initially screened 300,000 compounds and then synthesized more than 1,000 of them, and found a few that were likely to work in humans. We focused on the most effective. We think we now have something very promising.”
“十年前我们就确定了这个药物的分子靶点，但是寻找一种高效阻断靶点的方法却耗费了我们将近十年的时间，”芝加哥大学医学教授兼芝加哥大学个体化治疗中心副主任——Yusuke Nakamura（MD与PhD）说道。“最初我们筛选了300，000个化合物然后合成了其中的1，000多种，并发现有多个化合物可能在人体中发挥作用。我们重点关注了最高效的化合物。现在我们认为我们获得了十分有前景的东西。”
OTS964 targets TOPK (T – lymphokine-activated killer cell – originated protein kinase), a protein that is produced by a wide range of human cancers and is believed to promote tumor growth. High TOPK expression correlates with poor prognosis in patients with breast and lung cancer.
OTS964的靶点为TOPK（起源于T淋巴因子激活杀伤细胞的蛋白激酶），这是一种表达于多种人类癌症组织的蛋白质，人们相信它能促进肿瘤的生长。TOPK高表达与乳腺癌、肺癌患者的不良预后是有紧密联系的。
Initial studies of the drug, and a precursor called OTS514, found they were effective in killing cancer cells. But they could disrupt the production of new red and white blood cells, causing hematopoietic toxicity such as mild anemia and increasing the risk of infection. At the same time, the drugs increased the production of platelets, which help in blood clotting.
在最初的研究中，该药物与一种名为OTS514的先导化合物被发现具有显著的杀伤癌细胞的活性，但是他们能干扰红细胞和白细胞的生成，由此导致血液系统毒性，例如轻度贫血以及感染风险升高。与此同时，这两种药物能够促进血小板的生成，这是一种能促进凝血的物质。
When the researchers encapsulated the drugs in liposomes—microscopic bubbles similar to a cell membrane, commonly used to transport drugs within the body—the drug no longer caused this decrease in red and white blood cells. This approach “completely eliminated the hematopoietic toxicity,” the researchers wrote.
当研究人员们将药物包于脂质体中——类似于细胞膜的微球，广泛应用于药物的体内输送——药物则不再导致红细胞与白细胞的减少了。这种方法“彻底除去了血液系统毒性”，研究人员们如是写道。
They tested OTS964 alone and in liposomes in mice with a highly aggressive human lung tumor known as LU-99. They allowed the tumors to grow to 150 cubic millimeters—about the size of a raisin—and then administered the drug intravenously to six mice, twice a week for three weeks. The tumors shrank rapidly and continued to shrink even after treatment stopped. In five of the six mice, the tumors completely disappeared—three within 25 days of the first treatment and two within 29 days. Mice that received the liposome-coated drug had no detectable toxicity.
研究人员们单独测试了OTS964并将该药物包裹于脂质体中进入移植有人类高度恶性肺癌（LU-99）的小鼠体内。他们让肿瘤长到了150立方毫米的大小——接近一个葡萄干的体积——然后对6只小鼠进行为期3周、一周2次的静脉给药。6只小鼠中有5只小鼠的肿瘤完全消失了——3只在初步处理的25天内消失了，另外2只在29天内消失了。被给予脂质体药物的小鼠并没有显现出明显的毒性反应。
The drug also proved effective when taken in larger doses by mouth. Six mice with LU-99 lung tumors were fed 100 milligrams per kilogram of OTS964 every day for two weeks. Again, continuous tumor shrinkage was observed after the final dose of the drug. In all six mice the tumors completely regressed. All of the mice had low white-blood-cell counts after treatment, but they recovered within two weeks.
更大剂量口服给药被证明也是有效的。在2周的时间内，6只UL-99肺癌小鼠每天以100mg/kg的标准进行OTS964口服给药。重复上述步骤，直到在药物的最终剂量给药后观察到肿瘤缩小。6只小鼠的肿瘤都彻底衰亡了，所有的小鼠在治疗后都被检测出较低的白细胞含量，但是2周以后就恢复正常了。
Although this was a small study, the outcome was dramatic. Seeing these results was a “quite exciting moment,” said Nakamura, who stepped down from his role as Director in the Japanese Government's Office of Medical Innovation to join the faculty at the University of Chicago in April 2012. “It is rare to see complete regression of tumors in a mouse model,” he said. “Many drugs can repress the growth, but it is uncommon to see them eradicated. This has rarely been reported.”
尽管这是一个小型研究，但结果却是激动人心的。看到这个结果的时候“真是个令人振奋的时刻”，Nakamura说道，他在2012年4月时辞去日本政府医学创新办公室主任一职，成为了芝加哥大学教职工中的一员。“在小鼠模型中，肿瘤彻底衰亡是很罕见的，”他说。“很多药物能抑制肿瘤的生长，但是能摧毁它的药物是不同寻常的。这几乎从未被报导过。”
Similar studies of the drug’s effects on tumor cells growing outside the body enabled the researchers to videotape the process as the cancer cells died. TOPK appears to play a central role late in cytokinesis, the final stage in cell division. Dividing cancer cells would begin to separate into two new cells, but were unable to fully disconnect, retaining an intercellular bridge.
类似的研究——这种药物对体外生长的肿瘤细胞的影响使得研究人员们能够将肿瘤细胞死亡的过程录制下来。TOPK在细胞浆移动后期体现出核心作用，该时期是细胞分裂的终末期。此时癌细胞开始分裂成两个子细胞，但并不是彻底分开而是保留了细胞间桥。
“Without TOPK the cells can’t seem to divide; they can’t make the break,” Nakamura said. “They can’t complete the process. Instead they remain tethered by a tiny bridge. When that finally breaks apart, they can’t close the membrane. Everything within the cells spills out, they suffer and then die.”
“如果没有TOPK则无法看到细胞的分裂，因为子细胞之间无法断开，”Nakamura说道。“它们不能完成细胞分裂这个过程，而是通过微小的连结将彼此束缚在一起。当最后子细胞分离开时，它们的细胞膜无法闭合，所有的细胞内容物就会溢出，细胞因此受到损伤而死亡。”
TOPK may provide a good drug target for several types of cancer. This study involved primarily lung cancers, but the gene is frequently upregulated in breast, brain, liver, bladder and other solid tumors as well as certain types of leukemia. The researchers are working with oncologists at the University to begin a phase-1 clinical trial as soon as the fall of 2015.
TOPK也许将成为优秀的药物作用靶点来治疗多种癌症。这项研究涉及的主要是肺癌，但是这一基因在乳腺癌、脑癌、肝癌、膀胱癌等其他实体肿瘤以及某些类型的白血病中表达增强。研究人员们正与肿瘤学家们在芝加哥大学一起努力，最快在2015年到来之际开始此药物的I期临床试验。

临床实验结果期待中~~

这个药比较现实可行，值得期待。

期待好消息快点到来。。。

不知道这个出来能不能吃得起啊

谁去买来试一下，这个不知道临床要多久，不知道还等不等的到它