Proposed evidence criteria for identifying tumor transition windows.
| Evidence criterion | What it demonstrates | Examples of measurable readouts | Main limitation |
|---|---|---|---|
| Temporal evidence | Shows that the state changes over time rather than reflecting a static tumor feature | Serial biopsy, time-course single-cell profiling, longitudinal ctDNA/cfDNA dynamics, repeated imaging | Sampling frequency may miss short-lived states |
| Molecular-state evidence | Identifies therapy-induced changes in tumor-cell programs | Transcriptomic states, chromatin accessibility, DNA methylation, proteomic changes, metabolic markers | Molecular change alone does not prove vulnerability |
| Functional dependency evidence | Links the transition state to altered survival requirements | Drug-sensitivity testing, pathway inhibition, synthetic lethality assays, metabolic dependency testing | Often requires experimental validation beyond profiling |
| Trajectory evidence | Distinguishes reversible adaptation from stable resistance | Persister-state markers, clonal expansion, resistance mutations, epigenetic stabilization signatures | Boundaries between reversible and stabilized states may be gradual |
| Clinical detectability evidence | Indicates whether the window could be monitored in patients | ctDNA, cfDNA methylation, fragmentomics, CTCs, imaging biomarkers, integrated biomarker panels | Clinical thresholds and timing remain incompletely standardized |
| Therapeutic actionability evidence | Supports intervention during the window | Sequential therapy response, adaptive therapy trials, biomarker-guided treatment modification | Requires prospective clinical validation |
CTCs: circulating tumor cells; ctDNA: circulating tumor deoxyribonucleic acid.
During the preparation of this work, the authors used OpenAI image-generation tools to assist with the initial preparation of conceptual figure drafts. After utilizing the tool, the authors reviewed, revised, and finalized the figures as necessary and take full responsibility for the final content of the publication.
OAAE: Investigation, Writing—original draft. MMN: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Supervision. Both authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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This research received no external funding.
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