Detection of genomic mutations in blood and urine free circulating tumour DNA in patients with inoperable and metastatic lung adenocarcinoma harbouring an EGFR mutation in tissue: a UK pilot study.

Detection of genomic mutations in blood and urine free circulating tumour DNA in patients with inoperable and metastatic lung adenocarcinoma harbouring an EGFR mutation in tissue: a UK pilot study.
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DOI:
10.3389/fonc.2023.1197037
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发表时间:
2023
影响因子:
4.7
通讯作者:
Oltean, Sebastian
Oltean, Sebastian
中科院分区:
医学3区
文献类型:
--
作者:
Brooks, Helen;Li, Ling;Addeo, Alfredo;Stevens, Megan;Comins, Charles;Oltean, Sebastian

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分析癌症患者血液或尿液中循环肿瘤DNA (ctDNA)的方法的发展为诊断和预后以及评估治疗反应提供了宝贵的资源。肺癌在过去的几年中,随着几种EGFR抑制剂的使用,在治疗策略上发生了革命性的变化。然而,几乎无一例外地出现了对这些疗法的耐药性。在本文中,我们描述了一个试点,纵向研究20例患者确诊EGFR突变在肺癌组织活检。该研究的目的是确定血浆和/或尿液中的ctDNA是否可用于监测经证实的EGFR突变阳性非小细胞肺癌(NSCLC)患者在使用EGFR抑制剂治疗期间的EGFR突变状态。在6至16个月的时间里,每月收集血液和尿液。对每位患者的CtDNA进行分析,以确定是否存在几种已知的易导致对EGFR抑制剂产生耐药性的突变。我们已经证明,从血浆和尿液中连续监测ctDNA是可行的,并且患者愿意参与这一过程。我们还表明,纵向ctDNA监测可以在放射学和临床疾病进展之前发现耐药突变。
The development of methodologies to analyse circulating tumour DNA (ctDNA) in the blood or urine of cancer patients provides an invaluable resource that can be used for diagnosis and prognosis and to evaluate response to treatments. Lung cancer has seen in the last years a revolution in treatment strategy with the use of several classes of EGFR inhibitors. However, almost invariably, resistance to such therapies appears. In this paper, we describe a pilot, longitudinal study with 20 patients with confirmed EGFR mutations in tissue biopsy for lung cancer. The objective of the study was to determine whether ctDNA from plasma and/or urine could be used to monitor the EGFR mutational status of patients with confirmed EGFR mutation-positive non-small cell lung cancer (NSCLC) during treatment with EGFR inhibitors. Blood and urine were collected monthly over periods ranging from 6 to 16 months. CtDNA was analysed in each patient for the presence of several known mutations that predispose to resistance to EGFR inhibitors. We have proven that serial monitoring of ctDNA from both plasma and urine is feasible and that patients are willing to participate in this process. We have also shown that longitudinal ctDNA monitoring may detect resistance mutations before the development of radiological and clinical disease progression.
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