Department of Internal Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
Department of Radiation Oncology, Division of Cancer Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Int J Mol Sci. 2022 Aug 12;23(16):9006. doi: 10.3390/ijms23169006.
Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for advanced NSCLC. ctDNA technologies have also shown the ability to detect the emerging mechanisms of acquired resistance that evolve after targeted therapy. Furthermore, the detection of minimal residual disease (MRD) by ctDNA for patients with NSCLC after curative-intent treatment may serve as a prognostic and potentially predictive biomarker for recurrence and response to therapy, respectively. Finally, ctDNA analysis via mutational, methylation, and/or fragmentation multi-omic profiling offers the potential for improving early lung cancer detection. In this review, we discuss the role of ctDNA in each of these capacities, namely, for molecular profiling, treatment response monitoring, MRD detection, and early cancer detection of NSCLC.
非小细胞肺癌（NSCLC）临床实践的进展正在将治疗模式转向越来越个性化的方法。利用各种循环分析物进行液体活检为采样肿瘤细胞内的分子含量提供了微创方法。血浆衍生的循环肿瘤 DNA（ctDNA）是无细胞 DNA（cfDNA）中肿瘤来源的成分，是研究最广泛的分析物，在 NSCLC 的临床管理中有越来越多的应用。作为肿瘤基因分型的替代方法，通过 ctDNA 评估致癌驱动因素改变已通过单基因聚合酶链反应（PCR）和下一代测序（NGS）成为晚期 NSCLC 的一种公认的伴随诊断方法。ctDNA 技术还显示出检测靶向治疗后出现的获得性耐药新兴机制的能力。此外，在根治性治疗后，通过 ctDNA 检测 NSCLC 患者的微小残留病（MRD）可能分别作为复发和对治疗反应的预后和潜在预测生物标志物。最后，通过突变、甲基化和/或片段化多组学分析进行 ctDNA 分析有可能提高早期肺癌的检测率。在这篇综述中，我们讨论了 ctDNA 在这些方面的作用，即用于分子谱分析、治疗反应监测、MRD 检测和 NSCLC 的早期癌症检测。
