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

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

doi:10.1016/j.tcb.2024.11.007

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

Trends Cell Biol. 2024 Dec 26:S0962-8924(24)00249-6. doi: 10.1016/j.tcb.2024.11.007. Online ahead of print.

Authors

Shervin Tabrizi¹, Carmen Martin-Alonso², Kan Xiong³, Sangeeta N Bhatia⁴, Viktor A Adalsteinsson³, J Christopher Love⁵

Affiliations

¹ 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. Electronic address: shervin@broadinstitute.org.
² 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.
³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Wyss Institute at Harvard University, Boston, MA, USA; Howard Hughes Medical Institute, Cambridge, MA, USA.
⁵ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

PMID: 39730275
DOI: 10.1016/j.tcb.2024.11.007

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.

Publication types

Review