For anyone touched by cancer — as a patient, caregiver, or clinician — the promise of a simple blood draw replacing or supplementing invasive tissue biopsies represents a meaningful shift in how treatment decisions get made. Liquid biopsy technology, particularly the detection of circulating tumor DNA (ctDNA), is moving from research curiosity to clinical infrastructure, and understanding what it can and cannot yet deliver matters enormously.
This narrative review published in JAMA synthesizes the current state of ctDNA-based liquid biopsies across three primary clinical applications: monitoring disease progression in real time, detecting minimal residual disease (MRD) — microscopic cancer remaining after treatment — and identifying targetable genetic variants that inform therapy selection. Unlike conventional tissue biopsies, which capture a single tumor snapshot, ctDNA sampling can theoretically reflect tumor heterogeneity across multiple sites simultaneously. The review highlights how ctDNA assays are increasingly being integrated into oncology workflows for cancers including colorectal, lung, and breast, where FDA-cleared tests now exist for specific clinical indications.
Contextualizing this within the broader landscape, liquid biopsies have been advancing for over a decade, but clinical translation has been uneven. The core technical challenge — sensitivity versus specificity — remains unresolved for early-stage cancers, where tumor-shed DNA circulates at extremely low fractions. False-negative rates in early detection contexts are still a meaningful limitation, and clonal hematopoiesis (non-tumor-derived circulating DNA mutations) continues to complicate interpretation. MRD detection post-surgery is arguably the most clinically mature application, with prospective data in colorectal and lung cancers suggesting ctDNA positivity predicts recurrence months before imaging. For treatment selection, ctDNA-identified resistance mutations — such as EGFR T790M in lung cancer — are already standard of care in some settings. This review is confirmatory and synthesizing rather than paradigm-shifting, but it serves as a useful clinical benchmark for where the field stands heading into broader real-world deployment.