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

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

Affiliations
Review

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

Shervin Tabrizi et al. Trends Cell Biol. 2025 Jun.

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.

Keywords: biomarkers; cfDNA clearance; cfDNA shedding; ctDNA.

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Conflict of interest statement

Declaration of interests The authors are listed as inventors on a patent related to improving cfDNA recovery (PCT/US2022/013769). J.C.L., V.A.A., and S.N.B. are cofounders of Amplifyer Bio. C.M.A. is an employee of Amplifyer Bio. J.C.L. has interests in Sunflower Therapeutics PBC, Honeycomb Biotechnologies, OneCyte Biotechnologies, QuantumCyte, and Repligen, which were not involved in this work. V.A.A. is a coinventor on a patent application (US 2023/0203568, pending) licensed to Exact Sciences and receives research funding from Exact Sciences. S.N.B. reports consulting roles and/or equity in Sunbird Bio, Satellite Bio, Catalio Capital, Port Therapeutics, Matrisome Bio, Xilio Therapeutics, Ochre Bio, Vertex Pharmaceuticals, Ropirio Therapeutics, Danaher, and Owlstone Medical, which were not involved in this work. J.C.L.’s and S.N.B.’s interests were reviewed and managed under MIT’s policies for potential conflicts of interest.

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