Circadian Clock Crosswalk Between Chronic Disease and Antitumor Response

Circadian disruption is increasingly recognized as a contributing factor in both chronic disease and impaired antitumor immunity; however, these two fields have largely evolved independently. We conducted a Scale for the Assessment of Narrative Review Articles-guided narrative review of PubMed, Scopus, and Google Scholar covering the period from 1993 through 2026, screening 550 records and critically appraising 167 eligible studies across five circadian mechanisms: immune, metabolic, oxidative-genomic, neuroendocrine, and tumor-intrinsic regulation. Core clock components, including BMAL1, CLOCK, and the Period and Cryptochrome gene families, coordinate cell-cycle progression, DNA repair, metabolic flux, and immune oscillation. Disruption of these mechanisms compromises tissue homeostasis and antitumor surveillance. Circadian misalignment promotes inflammation, oxidative stress, and metabolic dysregulation associated with cardiometabolic, neurodegenerative, and respiratory diseases, while the same mechanisms remodel the tumor microenvironment and reduce tumor-infiltrating lymphocytes in preclinical models. Clinical evidence in cancer remains preliminary and is derived largely from retrospective cohorts and clinical trials demonstrating improved treatment tolerability rather than survival benefit. Interventions that restore circadian alignment—including timed light exposure, time-restricted eating, and structured sleep schedules—have demonstrated benefits in randomized trials for selected chronic conditions, whereas cancer chronotherapy remains largely at the preclinical stage. Overall, circadian biology represents a mechanistic crosswalk linking chronic disease susceptibility with antitumor immune regulation. Future priorities include the development of standardized biomarkers of circadian disruption, prospective immunotherapy-timing trials powered to assess survival outcomes, and the expansion of chronotherapy protocols to cancer types that remain unexplored.