ReviewCancers2026
Predictive Biomarkers of Metronomic Chemotherapy Response in Solid Tumors: Chasing an Elusive Signal.
Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetronomic chemotherapy (MCT), understood as continuous, low-dose cytotoxic administration without prolonged drug-free intervals, has become an established strategy in several solid tumors, acting primarily through antiangiogenic, immunomodulatory, and direct cytostatic mechanisms rather than replication-dependent cytotoxicity. Despite an expanding evidence base, including positive randomized trials, validated predictive biomarkers of response remain unavailable.
methodsWe searched PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2000 to July 2026) for phase II/III randomized trials, prospective cohorts, and selected retrospective analyses of MCT in breast cancer, head and neck squamous cell carcinoma, NSCLC, and mCRC, and extracted biomarker data from embedded translational substudies of eligible trials.
resultsIn breast cancer, phase III SYSUCC-001 (adjuvant metronomic capecitabine, improved DFS in TNBC) and MECCA (metronomic capecitabine plus aromatase inhibitor in HR+/HER2- disease) provide the strongest evidence, supported by randomized phase II data for the VEX regimen (METEORA-II) and MCT-anti-PD-1 combinations. TEMPO LUNG established metronomic vinorelbine as effective in platinum-unfit NSCLC, while CAIRO3 confirmed metronomic capecitabine-bevacizumab as an effective mCRC maintenance therapy. Most recently, the phase III TMC-I trial extended positive randomized evidence to head and neck cancer. Candidate biomarkers span angiogenic, immune, tumor proliferative, molecular, pharmacodynamic cytokine, on-treatment clinical (adverse-event-based), and gut-microbiome domains, with FOXC1, circulating endothelial cell kinetics, VEGF pathway markers, and regulatory T-cell dynamics among the most promising; however, none has been prospectively validated in a dedicated confirmatory trial.
conclusionsMCT has moved from empirical use to an evidence-based strategy across multiple tumor types, but the lack of validated predictive biomarkers limits informed patient selection. Future trials should incorporate biomarker-driven designs, particularly FOXC1, endothelial cell kinetics, and immune profiling as co-primary objectives. Defining an MCT-sensitive biological phenotype remains the key translational challenge for the field.
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