Nature Medicine Review Positions Liquid Biopsy Across the Full Cancer Care Continuum
This 2025 review surveys the evolution of cfDNA analysis from targeted mutation panels to whole-genome and epigenome sequencing combined with AI, and maps clinical applications from screening through treatment monitoring to MRD detection. The authors identify reliable sampling of rare ctDNA fragments as the central technical challenge and call for prospective validation of ctDNA burden as a clinical decision tool. The paper provides a comprehensive framework for integrating liquid biopsy into routine oncology workflows.
The original study
Liquid biopsies across the cancer care continuum.
- Authors
- Landon BV, Annapragada AV, Niknafs N, Velculescu VE, Anagnostou V
- Journal
- Nature medicine
- Type
- Journal Article, Review
- PMID
- 41372534
Original abstract
Liquid biopsies have the potential to transform precision oncology by enabling the sensitive and timely detection of cancer across various clinical settings. Minimally invasive analyses of circulating cell-free DNA (cfDNA) have emerged as cutting-edge approaches for cancer detection, characterization and monitoring. Early efforts focused on mutation-based targeted sequencing, whereas newer methods use whole-genome and epigenome sequencing combined with artificial intelligence to broaden the range of alterations that can be assessed in cfDNA. Despite these advances, substantial technical and clinical challenges prevent widespread adoption. Key areas for improvement include achieving clinically meaningful detection sensitivities, enhancing assay accessibility and prospectively evaluating the clinical sensitivity of circulating tumor DNA burden in early and metastatic settings, to support the integration of liquid biopsies into therapeutic decision-making. Here we discuss technologies and analytical methodologies in cfDNA detection, together with their clinical validity and utility. We highlight opportunities to address key challenges and to support the implementation of liquid biopsies throughout the cancer care continuum.