Standardizing caloric restriction for preclinical cancer research

Despite increasing rates of metabolic syndrome, cancer treatment regimens often ignore the underlying metabolic dysfunction in patients. A high proportion of cancer patients have metabolic dysfunction, and caloric restriction has shown the potential to improve cancer treatment response. However, preclinical efficacy is hindered by inconsistent protocols. We demonstrated that a CR (caloric restriction) diet enhances radiotherapy outcome by promoting apoptosis and downregulating cell survival pathways in mice. However, CR animal models implementation greatly differs in previous cancer studies, hindering its clinical translation. Here, we propose an effective CR protocol that safely achieves a 30% caloric reduction in two weeks. Week one involves single housing the mice and taking individual caloric intake measurements across four days. Week two involves weaning the mice to a 30% reduction by reducing their caloric intake by 10% every other day, which allows for a safe reduction. This protocol integrates individualized intake measurement, gradual weaning, and real-time monitoring-features rarely combined in prior models-offering a reproducible and translationally relevant framework for cancer studies.