打开APP

Nature:美丽的误会?糖尿病药物或可用于治疗白血病

  1. 吡格列酮
  2. 慢性粒细胞白血病
  3. 糖尿病
  4. 肿瘤干细胞

来源:生物谷 2016-03-23 14:47

药物研发中总有各种千奇百怪的“意外”。如果不是弗莱明在培养基上多看了一眼,或许青霉素的发现还会推迟许多年。而这些美丽的“意外”往往会进一步推动人类的进步。最近,一个国际研究团队就发现以往用于治疗糖尿病的药物——吡格列酮或许能够帮助人类更好的对抗白血病。

2015年9月7日讯 /生物谷BIOON/ --药物研发中总有各种千奇百怪的“意外”。如果不是弗莱明在培养基上多看了一眼,或许青霉素的发现还会推迟许多年。而这些美丽的“意外”往往会进一步推动人类的进步。最近,一个国际研究团队就发现以往用于治疗糖尿病的药物——吡格列酮或许能够帮助人类更好的对抗白血病。

慢性粒细胞白血病(CML)是一种罕见疾病,每年英国境内有600人被诊断患有这种疾病。尽管市面上有数种畅销疗法,但并不适用于所有患者。此外,有的患者还会对这些疗法产生抗性。

在这一研究中,24名CML患者接受了吡格列酮结合传统疗法的联合治疗,这些患者此前都接受了传统药物治疗,但白细胞总数仍然超标。12个月后,有超过50%的患者对这一疗法进行响应,其中最先响应的三名患者在接下来的五年中疾病没有复发。这一现象使得研究人员大为振奋,研究人员希望未来这一结果也能适用于其他类型的肿瘤。

CML患者体内患者血液中白细胞数量异常增生,长此以往会导致患者血液中血小板、红细胞等其他细胞数目骤减,从而使患者无法正常抵抗外界细菌等有害物质的侵害。来自英国癌症研究中心的Prof Peter Johnson认为,尽管近几年来随着伊马替尼等新药问世,CML患者的生存状况已经获得极大改观,但是仍有部分患者对这些药物并不响应甚至产生抗性。这项研究则向我们展示了通过深入了解肿瘤干细胞机制对新药开发的深远意义。不过,这一研究也只是在小部分患者群体中进行的,如果将患者群体规模扩大,吡格列酮是否还能有如此效果还是个问题。

同时,其他科学家也指出,吡格列酮存在的副作用也是这一疗法最终能否走上临床的一个重点。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。更多资讯请下载生物谷APP.

生物谷推荐的原文链接和英文摘要:

Diabetes drug may help in leukaemia

Nature    doi:10.1038/nature15248

Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists

Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology1. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR–ABL2. During the chronic phase, this sole genetic abnormality (chromosomal translocation Ph+: t(9;22)(q34;q11)) at the stem cell level causes increased proliferation of myeloid cells without loss of their capacity to differentiate. Without treatment, most patients progress to the blast phase when additional oncogenic mutations result in a fatal acute leukaemia made of proliferating immature cells. Imatinib mesylate and other tyrosine kinase inhibitors (TKIs) that target the kinase activity of BCR–ABL have improved patient survival markedly. However, fewer than 10% of patients reach the stage of complete molecular response (CMR), defined as the point whenBCR-ABL transcripts become undetectable in blood cells3. Failure to reach CMR results from the inability of TKIs to eradicate quiescent CML leukaemia stem cells (LSCs)2, 3, 4. Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ(PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs. When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool.

 

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->