奥希替尼目前作为EGFR突变非小细胞肺癌的一线治疗药物，耐药性的出现带来了实质性挑战。多基因组液体活检可以检查分子机制和早期耐药诊断的可能性。我们使用分子条形码文库构建试剂盒（Archer® LiquidPlex™），可以使用游离 DNA 分析多个癌症相关基因来自患者的血浆样本。我们在不同时间点连续采集了我院17名肺腺癌患者的血浆，提取游离DNA并进行LiquidPlex分析。血浆DNA浓度与奥希替尼耐药的存在与否无关。使用二代测序在耐药标本中检测到的病理突变为MAP2K1、PIK3CA、TP53、BRAF和EGFR。在复发病例中，4例（平均88天）在确诊复发前6个月内检测到初诊时发现的EGFR突变。许多在液体活检中未检测到已知 EGFR 突变的复发病例显示，检测到复发与最后一次抽血进行液体活检之间的间隔较长（平均 255 天）。频繁的液体活检有助于识别已知的 EGFR 突变，例如早期检测复发的标志物。观察到多种癌症驱动突变，表明一线奥希替尼治疗的肺腺癌存在多种耐药机制。版权所有 © 2023，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

Osimertinib is currently used as a first-line treatment for EGFR-mutated non-small cell lung cancer, and the emergence of drug resistance poses a substantial challenge. Liquid biopsy with a multi-gene panel can examine both the molecular mechanisms and possibility of early resistance diagnosis.We used a molecular barcode library construction kit (Archer® LiquidPlex™) that allowed the analysis of multiple cancer-related genes using cell-free DNA from the plasma samples of patients. We collected plasma from 17 consecutive patients with lung adenocarcinoma at our hospital at various time points and cell-free DNA was extracted and subjected to LiquidPlex analysis.Plasma DNA concentration was not associated with the presence or absence of resistance to osimertinib. The pathological mutations detected using next-generation sequencing in the resistant specimens were in MAP2K1, PIK3CA, TP53, BRAF, and EGFR. Among the recurrent cases, EGFR mutations identified at the initial diagnosis were detected within 6 months before relapse confirmation in four cases (average 88 days). Many of the recurrent cases without detection of known EGFR mutations in the liquid biopsy showed a longer interval between the detection of relapse and the last blood draw for the liquid biopsy (average 255 days).Frequent liquid biopsies are useful for identifying known EGFR mutations as markers for early detection of relapse. Several cancer driver mutations were observed, suggesting a variety of mechanisms of resistance in first-line osimertinib-treated lung adenocarcinoma.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.