The article examines how liquid biopsy is evolving from an alternative to tissue sampling into a tool for molecular insight, treatment guidance, and disease monitoring, with a focus on ctDNA and MRD studies presented at ASCO 2026.
Approach:
Longitudinal monitoring: Liquid biopsy can provide molecular information through serial blood sampling, complementing tissue testing when repeat biopsies are difficult or unavailable.
MRD assessment: The article describes ASCO 2026 studies evaluating circulating tumor DNA (ctDNA) after treatment as a marker of recurrence risk and disease status.
Multimodal analysis: Researchers are combining mutation detection with methylation profiling and fragmentomics to improve sensitivity and add biological context.
Diagnostic strategy: The article discusses whether diagnostics may need to assess pathway activity and tumor biology, rather than mutation status alone, as therapies broaden their targets.
Key Findings:
MONSTAR-SCREEN-3 analyses found that ctDNA positivity after curative-intent treatment was associated with significantly worse disease-free survival across multiple cancer types.
A PARTNER Phase 2/3 sub-study found post-treatment ctDNA positivity was highly prognostic for distant recurrence and outperformed pathologic complete response for risk stratification.
In the PREDICT-RD Phase 2 study in early triple-negative breast cancer, ctDNA surveillance detected MRD before clinical or radiographic evidence of relapse.
The RASolute 302 Phase III study reported daraxonrasib activity in previously treated metastatic pancreatic cancer across KRAS-mutant and non-mutant populations.
Interpretation:
The article describes a shift from episodic molecular testing toward longitudinal disease monitoring. It reviews ctDNA findings related to recurrence risk and MRD detection, explores combining mutation detection with methylation profiling and fragmentomics, and raises questions about the predictive value, cost, complexity, and implementation of multimodal testing.
Limitations:
The article raises unresolved questions about whether multimodal testing adds enough predictive power to justify its cost and complexity, whether benefits vary across cancer types, and whether testing can be implemented consistently across clinical laboratories.
The supplied context ends mid-sentence during discussion of KRAS-directed therapies.
Philip Marriott, Renée Webster, and Konstantinos Kouremenos revisit three investigations in which an additional dimension of separation provided the information needed to solve three very different analytical mysteries
