克服癌紫杉醇耐药

蛋白质组学研究揭示了一种蛋白，当被抑制，使癌症更容易化疗

2010年1月25日

波士顿，大众。——紫杉，一组癌症drugs that includes paclitaxel (Taxol®) and docetaxel (Taxotere®), have become front-line therapy for a variety of metastatic 癌症s。 But as with many chemotherapy agents, resistance can develop, a frequent problem in breast, ovarian, prostate and other 癌症s。 Now, 癌症 researchers at波士顿儿童医院report a protein previously unknown to be involved in taxane resistance and could potentially be targeted with drugs, making a 癌症 more susceptible to chemotherapy。

研究人员认为，这种蛋白质，Prohibitin1，也可以作为一种生物标志物，让医生用一个简单的血液测试预测患者对化疗的反应。这项研究是在网上发布的国家科学院学报在其在线早期版本在1月25日的一周。

这项研究由布鲁斯zetter，博士，，儿童血管生物学计划，用蛋白质组学技术比较紫杉醇敏感和紫杉醇耐药的人类肿瘤细胞株中的蛋白质。研究人员发现，耐药细胞株，但不敏感的细胞系，在其表面Prohibitin1。当他们抑制Prohibitin1 RNA干扰技术，肿瘤细胞对紫杉醇的变得更敏感，在细胞培养和小鼠活体植入紫杉醇耐药肿瘤。

Zetter's lab is still investigating why having prohibitin1 on the cell surface makes a tumor cell resistant to taxanes。 But in the meantime, he believes that not only could prohibitin1 be suppressed to overcome taxane resistance, but that it could also be exploited as a means of targeting chemotherapy selectively to resistant 癌症 cells。

"We are working to target various 癌症 drugs to taxane-resistant cells by attaching them to compounds that bind to prohibitin," Zetter explains。 One such compound is already known, and works well in animals to target other prohibitin-rich cells, but has yet to be tested in humans。

Suppressing prohibitin1 alone probably isn't enough to make a 癌症 fully Taxol-susceptible, but could be combined with other strategies aimed at increasing taxane susceptibility, such as targeting another protein called GST Pi, the researchers say。 Other mechanisms of resistance are known, but they so far haven't been shown to present effective targets for therapy。

Zetter's lab is also trying to develop prohibitin1 as a biomarker for taxane resistance that physicians could use in the clinic。 Since it's on the surface of the cell, Zetter believes prohibitin1 may circulate in the blood where it could easily be detected。 His lab is in talks with several 癌症 centers to obtain serum samples from patients who did and didn't respond to Taxol, so that prohibitin1 levels could be measured and compared。

zetter指出Prohibitin1可能很容易被忽视，并被发现是因为球队发生了特别观察在细胞膜的蛋白质，而不是单纯的做一个全细胞蛋白质组学分析。

“有趣的是抑制素不只是一个过度表达的蛋白，”zetter说。”它主要是在细胞表面上调。当我们看着整个细胞抑制素不是绝对量没有改变。相反，抑制素是从细胞内到细胞表面。它已经从一个位置移到另一个，当时，肿瘤细胞成为抗紫杉。事实上，它移动到细胞表面也使得它更容易直接药物。

波士顿儿童医院 has pending and issued international patents on this technology (for more information, seehttp:\/\/www。childrensinnovations。org\/searchdetails。aspx？标识= 1247）。

尼斯帕特尔，博士，是这项研究的第一作者。这项研究是由一项拨款资助的国立卫生研究院。

触点：
艾琳的长跑冠军
波士顿儿童医院
617-919-3110
erin。mccolgan@childrens。harvard。edu

Founded in 1869 as a 20-bed hospital for children, 波士顿儿童医院 today is one of the nation's leading pediatric medical centers, the primary pediatric teaching hospital of Harvard Medical School, and the largest provider of health care to Massachusetts children。 In addition to 396 pediatric and adolescent inpatient beds and more than 100 outpatient programs, Children's houses the world's largest research enterprise based at a pediatric medical center, where its discoveries benefit both children and adults。 More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community。 For more information about the hospital visit:www。childrenshospital。org/newsroom。

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