Figure 1.

Anticancer effects of reduced caloric intake. A decrease in caloric intake activates nutrient scarcity signaling pathways and triggers a global metabolic shift—toward catabolism and ketogenesis—as well as an integrated cellular stress response. Cell adaptations to the nutrient restriction-induced stress include autophagy, DNA repair, and antioxidant response at the systemic level. In consequence, circulatory procarcinogenic factors are downregulated: those include inflammatory factors such as IL1β, IL6, and CRP, but also metabolic regulators such as glucose, insulin, insulin growth factor-1 (IGF1), and leptin, which nurture the tumor microenvironment. Finally, calorie-restricted tumors are sensitized to oxidative stress, and autophagy induction favors ATP release, which in turn attracts activate dendritic cells (DCs) into the tumor bed, ultimately stimulating anticancer immune responses by CD8⁺ T cells. AMPK, AMP-activated protein kinase; EP300, E1A binding protein P300; FA, fatty acids; FGF21, fibroblast growth factor 21; HDL, high-density lipoprotein; HO-1, heme-oxygenase 1; LDL, low-density lipoprotein; mTORC1, mammalian target of rapamycin complex 1; SIRT1, sirtuin 1; SIRT3: sirtuin 3.