期刊
NATURE BIOMEDICAL ENGINEERING
卷 6, 期 3, 页码 232-245出版社
NATURE PORTFOLIO
DOI: 10.1038/s41551-021-00837-3
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资金
- NIH [P01CA163222, R01CA197486, R01CA233364, R01CA203964]
- CPRIT grant [RP180147]
This Review discusses the challenges and opportunities of technologies for the analysis of cell-free DNA for cancer diagnosis. It highlights the potential of cfDNA as biomarkers for guiding therapy, monitoring drug resistance, and early detection of cancers. However, the low concentrations and fragmented nature of cfDNA present challenges for clinical diagnostic applications. The Review describes state-of-the-art technologies and highlights the need to address biological and technical challenges to improve cancer diagnostics and patient care.
This Review discusses the challenges and opportunities, biological and technical, of technologies for the analysis of cell-free DNA for the diagnosis of cancer. Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, and for the early detection of cancers. However, the analysis of cfDNA for clinical diagnostic applications remains challenging because of the low concentrations of cfDNA, and because cfDNA is fragmented into short lengths and is susceptible to chemical damage. Barcodes of unique molecular identifiers have been implemented to overcome the intrinsic errors of next-generation sequencing, which is the prevailing method for highly multiplexed cfDNA analysis. However, a number of methodological and pre-analytical factors limit the clinical sensitivity of the cfDNA-based detection of cancers from liquid biopsies. In this Review, we describe the state-of-the-art technologies for cfDNA analysis, with emphasis on multiplexing strategies, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve cancer diagnostics and patient care.
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