Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent cancer with significant treatment-related side effects, necessitating innovative adjunct strategies. Shortterm fasting (STF), defined as 24–72 hours of caloric abstention, has emerged as a potential complementary approach to enhance cancer therapy outcomes. STF induces systemic metabolic changes, including reduced glucose, insulin, and IGF- 1 levels, inhibiting oncogenic pathways like PI3K/AKT/mTOR. This creates a differential stress resistance (DSR) effect, protecting normal cells while sensitizing cancer cells to chemotherapy and radiotherapy. STF also promotes oxidative stress, autophagic cell death, and immune modulation, including reduced regulatory T cells and enhanced cytotoxic T-cell activity, potentially improving immunotherapy efficacy. STF has shown promise in preclinical studies for enhancing tumor shrinkage, mitigating chemotherapy-induced toxicity, and reducing radiotherapy side effects like mucositis. While it offers significant benefits, careful patient selection and standardized protocols are essential to ensure safety, particularly for those with metabolic disorders or cachexia. Future research should explore biomarkers, optimized fasting protocols, and combinations with targeted therapies. STF represents a transformative strategy in OSCC treatment by integrating metabolic reprogramming, immune enhancement, and tumor sensitivity to optimize therapeutic outcomes.

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