Elazezy Maha, Joosse Simon A
University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Comput Struct Biotechnol J. 2018 Oct 9;16:370-378. doi: 10.1016/j.csbj.2018.10.002. eCollection 2018.
Precision medicine in the clinical management of cancer may be achieved through the diagnostic platform called "liquid biopsy". This method utilizes the detection of biomarkers in blood for prognostic and predictive purposes. One of the latest blood born markers under investigation in the field of liquid biopsy in cancer patients is circulating tumor DNA (ctDNA). ctDNA is released by tumor cells through different mechanisms and can therefore provide information about the genomic make-up of the tumor currently present in the patient. Through longitudinal ctDNA-based liquid biopsies, tumor dynamics may be monitored to predict and assess drug response and/or resistance. However, because ctDNA is highly fragmented and because its concentration can be extremely low in a high background of normal circulating DNA, screening for clinical relevant mutations is challenging. Although significant progress has been made in advancing the detection and analysis of ctDNA in the last few years, the current challenges include standardization and increasing current techniques to single molecule sensitivity in combination with perfect specificity. This review focuses on the potential role of ctDNA in the clinical management of cancer patients, the current technologies that are being employed, and the hurdles that still need to be taken to achieve ctDNA-based liquid biopsy towards precision medicine.
癌症临床管理中的精准医学可通过名为“液体活检”的诊断平台来实现。该方法利用检测血液中的生物标志物以达到预后和预测目的。癌症患者液体活检领域正在研究的最新血液标志物之一是循环肿瘤DNA（ctDNA）。ctDNA由肿瘤细胞通过不同机制释放，因此可以提供有关患者当前体内肿瘤基因组构成的信息。通过基于ctDNA的纵向液体活检，可以监测肿瘤动态，以预测和评估药物反应及/或耐药性。然而，由于ctDNA高度碎片化，且在正常循环DNA的高背景中其浓度可能极低，因此筛选临床相关突变具有挑战性。尽管在过去几年中ctDNA的检测和分析取得了重大进展，但当前的挑战包括标准化以及将现有技术提高到单分子灵敏度并兼具完美特异性。本综述重点关注ctDNA在癌症患者临床管理中的潜在作用、目前正在使用的技术，以及为实现基于ctDNA的液体活检以推动精准医学仍需克服的障碍。
