Intermittent fasting enhances cancer therapy via autophagy-dependent and independent mechanisms: Evidence and implications

Figure 1 Mechanisms of intermittent fasting in cancer prevention and therapy. This figure depicts the proposed multidimensional anti-cancer mechanisms of intermittent fasting (IF), integrating metabolic, immunological, endocrine, and epigenetic pathways. IF attenuates oxidative stress and DNA damage, suppresses insulin/insulin-like growth factor 1 signaling, enhances immune surveillance, and improves vascular function. Additional mechanisms include modulation of gut microbiota-derived metabolites, alignment of the circadian rhythm, favorable endocrine adaptations, and activation of key epigenetic regulators, such as sirtuins. These interconnected mechanisms collectively enhance responsiveness to cancer therapy, positioning IF as a promising adjunctive strategy in integrative oncology. ROS: Reactive oxygen species; Nrf2: Nuclear factor erythroid 2-related factor 2; IGF-1: Insulin-like growth factor 1; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; NK: Natural killer; IL: Interleukin; TNF: Tumor necrosis factor; CRP: C-reactive protein; SIRT: Sirtuin; CCL8: Chemokine (C-C motif) ligand 8; HIF: Hypoxia-inducible factor 1; BMAL1: Brain and muscle ARNT-like 1; CLOCK: Circadian locomotor output cycles kaput; PER2: Period circadian regulator 2; SCFA: Short-chain fatty acid; FXR: Farnesoid X receptor; GH: Growth hormone.

Figure 2 Proposed model for intermittent fasting -induced autophagy upregulation in cancer prevention and therapy. In experimental cancer models, intermittent fasting-induced autophagy acts as a cellular stressor that enhances differential stress resistance during chemotherapy, protecting normal cells while promoting selective cancer cell death and increasing the efficacy of specific chemotherapeutic agents. Several forms of intermittent fasting-associated, autophagy-mediated cancer cell death have been documented[53-56]. DSR: Differential stress resistance.