Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient.

Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient.
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实体瘤的快速蛋白质组学分析揭示了LSD1是末期癌症患者的药物靶标。

DOI:
10.1002/1878-0261.12326
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发表时间:
2018-08
期刊:
影响因子:
6.6
通讯作者:
Mann M
Mann M
中科院分区:
医学2区
文献类型:
--
作者:
Doll S;Kriegmair MC;Santos A;Wierer M;Coscia F;Neil HM;Porubsky S;Geyer PE;Mund A;Nuhn P;Mann M

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基于质谱(MS)的技术的最新进展现在将转化癌症蛋白质组学从一个想法转变为实践。在这里,我们提出了一个强大的蛋白质组学工作流程,用于分析临床相关的人类癌症组织,允许在几个小时的测量时间和几天的总周转时间内定量数千种肿瘤蛋白。我们将其应用于一个极其罕见的脐尿管癌的化疗难治性转移病例。肺转移和周围组织的定量比较显示了几种显著上调的蛋白质,其中包括赖氨酸特异性组蛋白去甲基化酶1(LSD 1/KDM 1A)。LSD 1是一种表观遗传调节因子,也是肿瘤学积极开发的目标。因此,临床癌症蛋白质组学可以快速有效地确定可行的治疗方案。虽然目前描述了一个单一的案例研究,我们设想,它可以广泛应用于其他患者在类似的条件。
Recent advances in mass spectrometry (MS)‐based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma. Quantitative comparison of lung metastases and surrounding tissue revealed several significantly upregulated proteins, among them lysine‐specific histone demethylase 1 (LSD1/KDM1A). LSD1 is an epigenetic regulator and the target of active development efforts in oncology. Thus, clinical cancer proteomics can rapidly and efficiently identify actionable therapeutic options. While currently described for a single case study, we envision that it can be applied broadly to other patients in a similar condition.
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