5月29日消息 - 环球医学据悉，发表在《细胞》杂志上的一项新研究显示，一种用于治疗精神分裂症的抗精神病药物可使癌症干细胞转变为威胁较小的细胞类型。

“你必须要找到真正对癌症干细胞具有选择性的东西，”该研究的第一作者、来自麦克马斯特大学的Mickie Bhatia说。“我们已经工作了一段时间，很难找到正确的方法。”

30年来癌症患者的生存期很大程度上并未改变，许多人推测更大的成功将会通过解决稀少的且对化疗耐药的癌症干细胞来取得。

与正常的干细胞不同，癌症干细胞拒绝分化为稳定的非分裂细胞类型。Bhatia的研究小组利用这种差异，在人类癌症干细胞与正常的人类干细胞中筛选对前者具有活性的化合物。

通过测试数百种化合物，他们确定了近20种可能对癌症干细胞具有特异性的药物。其中看上去最有希望的是一种抗精神病药——硫利达嗪，众所周知，该药以大脑中的多巴胺受体为靶点来治疗精神分裂症。这种药物并不会杀死癌症干细胞，而是促使其分化，从而耗尽自我更新的细胞池。

研究人员发现，硫利达嗪可在不影响正常血液干细胞的情况下杀死白血病干细胞。比较白血病与正常血细胞的蛋白质有助于解释这种特异性。白血病细胞的表面可表达多巴胺受体，而正常的造血干细胞则不会。他们发现，多巴胺受体也见于一些乳腺癌干细胞。

“这给了我们一些解释，”Bhatia说。这也表明，多巴胺受体可能可以作为稀少的癌症干细胞的生物标志物。

鉴于研究结果，Bhatia的小组已经计划对应用硫利达嗪（已获FDA批准）联合标准抗癌药物治疗急性髓细胞白血病展开临床试验。

“我们很兴奋将把这种药物带给患者，”Bhatia说。“我们也希望我们的平台现在可以成为筛选其他癌症干细胞药物的流水线。”（环球医学）

原文：

Schizophrenia Drug Differentiates Cancer Stem Cells into Less Threatening Cells

A new study published in the journal Cell reveals that an anti-psychotic drug that is used in treating schizophrenia can differentiate cancer stem cells into less threatening cell types.

"You have to find something that's truly selective for cancer stem cells," said Mickie Bhatia, lead author of the study from McMaster University. "We've been working for some time and it's hard to find that exact formula."

The survival of cancer patients is largely unchanged from 30 years ago, and many suspect that greater success will come by addressing the rare and chemotherapy-resistant cancer stem cells.

Unlike normal stem cells, cancer stem cells resist differentiating into stable, non-dividing cell types. Bhatia's team exploited this difference to simultaneously screen compounds for their activity against human cancer stem cells versus normal human stem cells.

By testing hundreds of compounds, they identified nearly 20 potential cancer stem cell specific drugs. The one that appeared most promising is an antipsychotic drug, thioridazine, which is known to work against schizophrenia by targeting dopamine receptors in the brain. The drug doesn't appear to kill cancer stem cells, but rather encourages them to differentiate, thus exhausting the pool of self-renewing cells.

The researchers showed that thioridazine kills leukemia stem cells without affecting normal blood stem cells. Comparing the proteins in leukemia versus normal blood cells helped to explain this specificity. The leukemia cells, but not normal blood stem cells, express a dopamine receptor on their surfaces. Dopamine receptors also appear on some breast cancer stem cells, they found.

"This gives us some explanation," Bhatia said. It also suggests that dopamine receptors might serve as a biomarker for rare, tumor-initiating cells.

In light of the findings, Bhatia's team is already planning for a clinical trial of the FDA-approved thioridazine in combination with standard anti-cancer drugs for adult acute myeloid leukemia.

"We're excited about bringing this drug to patients," Bhatia said. "We also hope our platform can now be a pipeline for other cancer stem cells drugs."
 

相关链接：http://www.medindia.net/news/schizophrenia-drug-differentiates-cancer-stem-cells-into-less-threatening-cells-101820-1.htm 

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