From:  Targeting tumor transition windows

 Translational requirements for clinical implementation of tumor transition-window strategies.

Translational requirementPractical meaningExample approachesMain barrier
Biomarker detectabilityThe transition state must be measurable during therapyctDNA, cfDNA methylation, fragmentomics, CTCs, imaging, single-cell profilingSensitivity, sampling timing, and assay standardization
Biological interpretabilityThe biomarker should reflect a meaningful tumor-state changePersister signatures, metabolic adaptation, pathway activation, resistance mutationsMolecular change may not prove vulnerability
Functional actionabilityThe detected state should be linked to a testable therapeutic dependencyDrug-sensitivity testing, pathway inhibition, synthetic lethality assaysRequires experimental or clinical validation
Clinical decision ruleBiomarker change must trigger a predefined treatment actionTreatment switching, sequencing, intensification, intermittent dosing adjustmentRisk of overtreatment if thresholds are weak
Trial validationThe strategy must improve outcomes compared with fixed therapyAdaptive trials, biomarker-guided randomization, serial monitoring endpointsRequires prospective testing and regulatory acceptance
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CTCs: circulating tumor cells; ctDNA: circulating tumor deoxyribonucleic acid.