Temporal data framework for tracking candidate tumor transition windows.
| Sampling point | Biological question | Data types | What it can reveal | Main limitation |
|---|---|---|---|---|
| Baseline before therapy | What tumor states exist before treatment? | Tumor biopsy, genomic profiling, single-cell profiling, ctDNA, imaging | Pre-existing heterogeneity, dominant clones, baseline pathway activity | Cannot distinguish pre-existing states from therapy-induced adaptation |
| Early on-treatment | How does the tumor initially respond to therapeutic pressure? | Serial biopsy, single-cell ribonucleic acid sequencing (scRNA-seq), single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq), ctDNA kinetics, cfDNA methylation, imaging | Early adaptive states, persister-like programs, stress-response activation | Short-lived states may be missed if sampling is too sparse |
| Response phase | Which adaptive states persist during tumor regression or stabilization? | ctDNA dynamics, CTC analysis, imaging, transcriptomic or epigenomic profiling | Residual disease, persister enrichment, metabolic or signaling compensation | Low tumor burden may reduce liquid biopsy sensitivity |
| Molecular progression | What resistance signals appear before clinical relapse? | ctDNA mutation tracking, cfDNA methylation, fragmentomics, serial imaging | Emerging resistant clones, epigenetic-state shifts, molecular relapse | Biomarker thresholds are not fully standardized |
| Clinical progression | Which resistant state has become stabilized? | Tumor biopsy, single-cell or spatial profiling, ctDNA, imaging | Fixed resistance mechanisms, clonal expansion, lineage switching | Later sampling may miss the earlier transition window |
| Post-progression reassessment | How should subsequent therapy be selected? | Integrated genomic, transcriptomic, epigenomic, proteomic, metabolic, and imaging data | New therapeutic dependencies and resistance architecture | Requires complex multi-omics integration and 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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