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恶性间皮瘤生物标志物:从发现到用于临床实践中的诊断、监测、筛查和治疗。

Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment.

机构信息

National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia; Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia; Department of Respiratory Medicine, Nedlands, WA, Australia.

出版信息

Chest. 2017 Jul;152(1):143-149. doi: 10.1016/j.chest.2016.12.004. Epub 2016 Dec 19.

Abstract

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.

摘要

恶性胸膜间皮瘤是一种与石棉暴露相关的高度侵袭性肿瘤。间皮瘤的有效治疗选择很少,患者的预后非常差,从诊断到中位生存期<12 个月。生物标志物已被提议作为癌症管理的一种具有成本效益的手段,过去 30 年来一直在寻找间皮瘤的生物标志物。在此期间,已经评估了许多传统的可溶性(糖)蛋白生物标志物,并且越来越多的信使 RNA、DNA、microRNA 和抗体等新型生物标志物正在从生物标志物发现项目中报告。迄今为止,可溶性间皮素是唯一获得美国食品和药物管理局批准用于间皮瘤临床应用的肿瘤生物标志物。间皮素是一种正常表达在间皮细胞表面的糖蛋白,在癌变状态下,它可以存在于循环中。间皮素在正常的非恶性组织中表达有限,因此是间皮素阳性肿瘤的一个有吸引力的治疗靶点。在这篇综述中,我们将重点介绍间皮素的发现和临床应用,并提供其他间皮瘤生物标志物的最新信息,并展示这些生物标志物研究如何在未来影响这种致命肿瘤的管理。

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