Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Semin Oncol. 2017 Oct;44(5):330-346. doi: 10.1053/j.seminoncol.2018.01.009. Epub 2018 Feb 3.
Circulating tumor DNA (ctDNA) consists of cell-free DNA (cfDNA) fragments that are released from tumor cells into the bloodstream. ctDNA harbors cancer-specific genetic and epigenetic alterations that allow its detection and quantification using a variety of emerging techniques. The promise of convenient non-invasive access to the complex and dynamic molecular features of cancer through peripheral blood has galvanized translational researchers around this topic with compelling routes to clinical implementation, particularly in the post-treatment surveillance setting. Although analysis methods must contend with the small quantities of ctDNA present in most patients, and the relative over-abundance of background cfDNA derived from normal tissues, recent technical innovations have led to dramatic improvements in the sensitivity of ctDNA detection. As a result, ever more studies are investigating the clinical utility of ctDNA for applications in (1) treatment response assessment, (2) identification of emerging resistance mechanisms, (3) minimal residual disease detection, and (4) characterization of clonal heterogeneity and selection. In this review, we describe the detection methods currently used in clinical studies to assess low fractions of ctDNA, as well as their utility in the applications previously described. Finally, we address current limitations that have hampered the clinical implementation of ctDNA analysis for post-treatment surveillance and propose steps that could be made to address them.
循环肿瘤 DNA（ctDNA）由从肿瘤细胞释放到血液中的无细胞 DNA（cfDNA）片段组成。ctDNA 携带有肿瘤特异性的遗传和表观遗传改变，这使其能够使用各种新兴技术进行检测和定量。通过外周血方便地非侵入性地获取癌症复杂和动态的分子特征的前景，激发了围绕这个主题的转化研究人员，为临床实施提供了引人注目的途径，特别是在治疗后监测环境中。尽管分析方法必须应对大多数患者中存在的少量 ctDNA，以及来自正常组织的相对过多的背景 cfDNA，但最近的技术创新导致了 ctDNA 检测灵敏度的显著提高。因此，越来越多的研究正在调查 ctDNA 在以下应用中的临床实用性：（1）治疗反应评估，（2）识别新出现的耐药机制，（3）微小残留病灶检测，以及（4）克隆异质性和选择的表征。在这篇综述中，我们描述了目前在临床研究中用于评估低分数 ctDNA 的检测方法，以及它们在前面描述的应用中的效用。最后，我们讨论了当前阻碍 ctDNA 分析在治疗后监测中临床实施的限制，并提出了可以解决这些限制的步骤。
