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调控游离DNA生物学作为液体活检的下一个前沿领域。

Modulating cell-free DNA biology as the next frontier in liquid biopsies.

作者信息

Tabrizi Shervin, Martin-Alonso Carmen, Xiong Kan, Bhatia Sangeeta N, Adalsteinsson Viktor A, Love J Christopher

机构信息

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Radiation Oncology, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

出版信息

Trends Cell Biol. 2025 Jun;35(6):459-469. doi: 10.1016/j.tcb.2024.11.007. Epub 2024 Dec 26.

DOI:10.1016/j.tcb.2024.11.007
PMID:39730275
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145268/
Abstract

Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase. To accomplish this, new methods to modulate the biological processes that govern cfDNA production, trafficking, and clearance in the body are needed, informed by a deeper understanding of cfDNA biology. Successful development of such methods could enable a major leap in the performance of liquid biopsies and vastly expand their utility across the spectrum of clinical care.

摘要

过去二十年的技术进步使得能够在生物样本中可靠地检测游离DNA(cfDNA)。然而,要充分发挥液体活检的潜力,还需要更高的临床灵敏度。这篇观点文章认为,为了克服当前的局限性,需要增加样本中收集到的信息丰富的cfDNA分子(如循环肿瘤DNA(ctDNA))的数量。为此,需要新的方法来调节体内控制cfDNA产生、运输和清除的生物学过程,这需要对cfDNA生物学有更深入的了解。成功开发此类方法可能会使液体活检的性能实现重大飞跃,并极大地扩展其在临床护理领域的应用。

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GWAS shows the genetics behind cell-free DNA and highlights the importance of p.Arg206Cys in DNASE1L3 for non-invasive testing.GWAS 揭示了游离 DNA 的遗传学基础,并强调了 DNASE1L3 中 p.Arg206Cys 对非侵入性检测的重要性。
Cell Rep. 2024 Oct 22;43(10):114799. doi: 10.1016/j.celrep.2024.114799. Epub 2024 Sep 25.
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ctDNA-based molecular residual disease and survival in resectable colorectal cancer.基于 ctDNA 的分子残留疾病与可切除结直肠癌的生存。
Nat Med. 2024 Nov;30(11):3272-3283. doi: 10.1038/s41591-024-03254-6. Epub 2024 Sep 16.
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DNA-sensing inflammasomes cause recurrent atherosclerotic stroke.DNA 感应炎性小体导致复发性动脉粥样硬化性卒中。
Nature. 2024 Sep;633(8029):433-441. doi: 10.1038/s41586-024-07803-4. Epub 2024 Aug 7.
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