新型高效抗癌药物 OST9640 O# L; `+ c, l b) q! `' G' H! E% K
http://www.yuaigongwu.com/forum.php?mod=viewthread&tid=20019, j8 K2 S W/ `/ v E
图注：OTS964脂质体进入癌症细胞，阻断TOPK酶，阻止细胞分裂的最后阶段。+ |) C7 n7 a: `* P
拍摄：Jae-Hyun Park博士，副教授，芝加哥大学血液肿瘤科6 ?/ X! Q" _) v$ |, i* x
《科学·转化医学》期刊（Science Translational Medicine）于2014年10月22日报道了芝加哥大学研究人员在Yusuke Nakamura教授的带领下研制出的一种名为OTS964的新型药物。该药物具有通过抑制一种在肺癌、乳腺癌等癌症中过量表达但正常组织中几乎不表达的蛋白质的活性，使癌细胞不能完成细胞分裂，进而促进癌细胞死亡的功能，小鼠试验证实对侵袭性人类肺癌具有良好的治疗效果。% U8 M4 i# t9 Z
早在十年前，研究人员就找到了OTS964的靶分子，但花了近10年的时间来找到抑制它的一种有效方法。在最初筛选的30万种复合物中，研究人员合成了1 000多种，并且从中找到了对人类最有效、非常有前景的几种。TOPK（T originated protein kinase，T细胞起源蛋白激酶）在细胞分裂晚期起到重要作用，能促进肿瘤生长，其高表达导致病人预后不佳。没有TOPK，细胞在分裂晚期不能形成闭合的细胞膜，因此细胞内物质外溢，导致细胞死亡。TOPK的表达在乳腺癌、脑癌、肝癌、膀胱癌和其他实性肿瘤，以及几种白血病中的表达都被上调了，是一个非常好的OTS964靶标。' k( J, _2 b( Y* ^1 ]
最初关于OTS964及其前体OTS964的研究发现，它们在癌症细胞的清除方面非常有效，但是会破坏新的红细胞和白细胞的产生，导致造血毒性（如轻度贫血），增加感染的风险，还会使血小板增多，促进血液凝固。将药物包裹在脂质胶囊中，它将不再引起红细胞和白细胞的减少。这种方法完全消除了造血毒性。OTS964可以口服，也可以静脉注射。口服的时候毒性小，耐受性良好。静脉注射时，该药物通过一种脂质载体来转运，药效与口服一样好，但副作用更小。小鼠实验证实，这两种方式都能完全抑制移植性肿瘤（transplanted tumors）。
% E7 B; o- A G% O) {% lNakamura教授认为，通常许多药物都能抑制肿瘤生长，但在小鼠模型中看到肿瘤完全消失是非常罕见的。2015年秋季，研究人员将与肿瘤专家一起开展I期临床试验。
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参考文献
2 i) K. a; h3 z2 x, Y! yYo Matsuo, Jae-Hyun Park, Takashi Miyamoto, Shinji Yamamoto, Shoji Hisada, Houda Alachkar, and Yusuke Nakamura. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Science Translational Medicine, October 2014 DOI:10.1126/scitranslmed.3010277, W2 s: k% }" r1 P2 |: ^
7 h( f2 t( _: d" f! @http://www.mnn.com/health/fitnes ... ancer-set-for-human
& W+ l( q1 J6 \# SNew miracle pill can completely eradicate cancer, set for human trials% F" w' n, B% P8 o1 G0 [
Cancer cure: 5 out of 6 mice transplanted with human cancers showed complete regression after receiving the drug, and with little to no side effects.
! _/ x% {6 V* KBy: Bryan Nelson
2 w- @3 k! j! E' e m" g$ ]$ uMon, Oct 27, 2014 at 09:22 PM* g( ]$ v" G0 K+ H# c
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Lung cancer is one of the cancers this drug can most effectively treat. (Photo: James Heilman, MD/Wiki Commons)) Y' ]$ ~( V8 A( v; x
A highly effective new drug, known as OTS964, could be the miracle cure for certain kinds of cancer that we've all been waiting for. The medication, which can be taken via a simple pill or through injection, has been shown to completely eradicate cancers that have been transplanted into mice, reports MedicalXpress. Human trials are set to begin as early as next year.
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The drug works by inhibiting a protein called TOPK that several types of cancer, such as lung and breast cancer, require to properly divide. Since the protein is rarely expressed in healthy, non-cancerous cells, the treatment targets cancer cells specifically, so there are very few — if any — negative side effects.
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/ ?, f5 a2 N% Q" n5 v; s6 s"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. "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." / q6 A! b4 M5 Q
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So far the drug has only been used in mice, but the mice were harboring human cancer cells. After being administered OTS964 intravenously twice a week for three weeks, the tumors disappeared completely for 5 of 6 mice within a month of their first treatment. The drug was even more effective when taken in pill form, curing the cancer in all of the mice. Mice that took the drug via mouth showed a reduced white blood cell count at the end of the trial period, but all of them recovered fully within two weeks. # d8 X' [. r& Q6 Q' b
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Seeing these results was a "quite an exciting moment," said Nakamura. "It is rare to see complete regression of tumors in a mouse model. Many drugs can repress the growth, but it is uncommon to see them eradicated."+ d: T1 A) b5 {
) W( ?( Q+ I8 n3 ]! R" b+ \The study looked primarily at lung cancers, but there is good reason to believe the drug will also be effective on other cancers that also rely on TOPK to divide properly, such as breast, brain, liver and bladder tumors. It may even work against certain types of leukemia. But the drug's effect on these other cancers is still speculative, pending further research. ! X0 }, u. M' t8 G2 }4 h5 {
1 }( M4 r6 k2 x. T! RThough this initial study was small, its success means phase-1 clinical trials can begin as soon as the fall of 2015.
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