Circulating cell-free DNA for non-invasive cancer management

  • Caitlin M. Stewart
    Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA

    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  • Dana W.Y. Tsui
    Corresponding author at: Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA.
    Marie-José and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA

    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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      • Cell-free nucleic acids in body fluids contain tumour fragments that can be profiled for prognostic and diagnostic information for the management of cancer.
      • cfDNA molecular profiling techniques, such as droplet digital PCR and next-generation sequencing, can be used to non-invasively guide treatment, track tumour evolution, detect the acquisition of resistance and monitor minimal residual disease.
      • cfDNA assays are now available for clinical use and more are rapidly being developed.
      Cell-free DNA (cfDNA) was first identified in human plasma in 1948 and is thought to be released from cells throughout the body into the circulatory system. In cancer, a portion of the cfDNA originates from tumour cells, referred to as circulating-tumour DNA (ctDNA), and can contain mutations corresponding to the patient's tumour, for instance specific TP53 alleles. Profiling of cfDNA has recently become an area of increasing clinical relevance in oncology, in particular due to advances in the sensitivity of molecular biology techniques and development of next generation sequencing technologies, as this allows tumour mutations to be identified and tracked non-invasively. This has opened up new possibilities for monitoring tumour evolution and acquisition of resistance, as well as for guiding treatment decisions when tumour biopsy tissue is insufficient or unavailable. In this review, we will discuss the biology of cell-free nucleic acids, methods of analysis, and the potential clinical uses of these techniques, as well as the on-going clinical development of ctDNA assays.


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