Circulating tumor DNA: current challenges for clinical utility.
Circulating tumor DNA: current challenges for clinical utility.
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DOI：
10.1172/jci154941
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发表时间：
2022-06-15
影响因子：
15.9
通讯作者：
Park, Ben H.
中科院分区：
文献类型：
--
作者：
Dang, Donna K.;Park, Ben H.
癌细胞将裸露的DNA分子排放到血液循环中。这种循环中的肿瘤DNA(CtDNA)已经成为液体活组织检查的主要分析物，以了解癌症的突变情况。结合下一代测序，ctDNA可以作为肿瘤组织的替代底物，用于突变检测和伴随诊断目的。事实上，精准医学的最新进展使ctDNA能够迅速地用于指导治疗决策，以预测靶向治疗和免疫治疗的反应和耐药性。与传统的组织活检相比，使用ctDNA的一个优点是相对无创地获取外周血，允许进行简单、重复和连续的评估。目前使用ctDNA的大多数临床实践都在努力识别可用药和耐药突变，以指导全身治疗决定，尽管主要是在转移性疾病中。然而，更新的研究正在评估ctDNA作为治疗环境中最小残留疾病的标记和作为在普通人群中检测癌症的有用筛查工具的潜力。在这里，我们回顾了ctDNA和液体活检的历史，检测ctDNA的技术，以及使用ctDNA作为微小残留病的标志和作为一般的基于血液的癌症筛查工具的一些当前的挑战和限制。我们还讨论了开展严格的临床研究的必要性，以证明ctDNA在未来肿瘤学中的临床应用价值。
Cancer cells shed naked DNA molecules into the circulation. This circulating tumor DNA (ctDNA) has become the predominant analyte for liquid biopsies to understand the mutational landscape of cancer. Coupled with next-generation sequencing, ctDNA can serve as an alternative substrate to tumor tissues for mutation detection and companion diagnostic purposes. In fact, recent advances in precision medicine have rapidly enabled the use of ctDNA to guide treatment decisions for predicting response and resistance to targeted therapies and immunotherapies. An advantage of using ctDNA over conventional tissue biopsies is the relatively noninvasive approach of obtaining peripheral blood, allowing for simple repeated and serial assessments. Most current clinical practice using ctDNA has endeavored to identify druggable and resistance mutations for guiding systemic therapy decisions, albeit mostly in metastatic disease. However, newer research is evaluating potential for ctDNA as a marker of minimal residual disease in the curative setting and as a useful screening tool to detect cancer in the general population. Here we review the history of ctDNA and liquid biopsies, technologies to detect ctDNA, and some of the current challenges and limitations in using ctDNA as a marker of minimal residual disease and as a general blood-based cancer screening tool. We also discuss the need to develop rigorous clinical studies to prove the clinical utility of ctDNA for future applications in oncology.