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用于诊断非小细胞肺癌中与酪氨酸激酶抑制剂耐药相关的体细胞突变的游离循环DNA的分子分析

Molecular analysis of cell-free circulating DNA for the diagnosis of somatic mutations associated with resistance to tyrosine kinase inhibitors in non-small-cell lung cancer.

作者信息

Del Re Marzia, Vasile Enrico, Falcone Alfredo, Danesi Romano, Petrini Iacopo

机构信息

Department of Clinical and Experimental Medicine, Clinical Pharmacology Unit, Pisa University, Pisa, Italy.

出版信息

Expert Rev Mol Diagn. 2014 May;14(4):453-68. doi: 10.1586/14737159.2014.908120. Epub 2014 Apr 11.

Abstract

In non-small-cell lung cancer, the molecular diagnosis of somatic mutations is instrumental for the choice of the most appropriate treatment. However, despite an initial response, resistance to tyrosine kinase inhibitors occurs and thereafter tumors progress. For this reason, next generation inhibitors able to overcome acquired resistances are currently in development. Therefore, the identification of the molecular determinants of resistance is needed to adapt treatment accordingly. The analysis of circulating cell-free tumor DNA represents a powerful tool to monitor the somatic changes induced by treatment. This review focuses on the most recent advantages in the diagnosis of acquired resistance in circulating cell-free tumor DNA and underlines the strategies ready to be translated in the clinical practice.

摘要

在非小细胞肺癌中,体细胞突变的分子诊断有助于选择最合适的治疗方法。然而,尽管最初有反应,但对酪氨酸激酶抑制剂的耐药性仍会出现,随后肿瘤会进展。因此,目前正在开发能够克服获得性耐药的新一代抑制剂。因此,需要确定耐药的分子决定因素,以便相应地调整治疗方案。循环游离肿瘤DNA的分析是监测治疗引起的体细胞变化的有力工具。本综述重点介绍了循环游离肿瘤DNA中获得性耐药诊断的最新优势,并强调了准备在临床实践中应用的策略。

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