尽管在精准医学时代通过检测和治疗取得了显著进展，全球肺癌的发病率和死亡率依然居高不下。切除活检和组织病理学分析是当前肺癌诊断的黄金标准，然而这种方法存在侵入性，并且仅能评估能够物理提取的有限组织量。此外，由于肿瘤的异质性或肿瘤细胞稀少，肺活检容易产生误导性结果。遗憾的是，迄今为止还没有发现高特异性和高敏感性的肿瘤生物标志物，特别是用于早期肺癌的。液体活检是一种用于肺癌诊断、治疗和预后评估的创新方法，被认为是可行的辅助工具。循环肿瘤DNA（ctDNA），作为液体活检的主要靶点，已经成为监测肿瘤分子过程的最敏感工具之一。本综述侧重于肿瘤异质性，以阐明液体活检的优越性，并对其演变进行回顾性讨论。我们系统阐述了ctDNA的生物特性，介绍了ctDNA检测的方法，并总结了ctDNA分析在肺癌患者中的应用。最后，我们介绍了目前应用中ctDNA分析的缺点，并突出了其在肺癌领域的有前景的未来。版权所有 © 2023 Elsevier B.V. 发表。

Lung cancer maintains a high morbidity and mortality rate globally despite significant advancements in detection and therapy in the era of precision medicine. Excisional biopsy and histopathologic analysis, the current gold standards for lung cancer diagnosis, are intrusive and intrinsically confined to evaluating the limited amount of tissue that could be physically extracted. Furthermore, due to tumor heterogeneity or low tumor cellularity, lung biopsy is prone to producing misleading results. Unfortunately, there has been no major breakthrough in tumor biomarkers with high specificity and sensitivity, particularly for early-stage lung cancer. Liquid biopsy, an innovative method for the assessment of cancer, has been considered a feasible auxiliary tool for the diagnosis, treatment and prognosis of lung cancer. Circulating tumor DNA (ctDNA), the main target of liquid biopsy, has emerged as one of the most sensitive tools for monitoring tumor molecular processes. Herein, this review focuses on tumor heterogeneity to elucidate the superiority of liquid biopsy and retrospectively discuss its evolution. We systematically elaborate ctDNA biological characteristics, introduce methods for ctDNA detection, and provide a summary of how ctDNA analysis has been used in patients with lung cancer. Finally, we cover the drawbacks of ctDNA analysis in current applications and highlight its promising future in lung cancer.Copyright © 2023. Published by Elsevier B.V.