Chronotherapy in Oncology: Aligning Cancer Treatment with Biological Time

Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy-particularly with fluoropyrimidines, platinum compounds, and anthracyclines-show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care.