Calorie restriction and cancer: overview of mechanisms. Chronic exposure to a calorie restriction regimen results in reduced circulating levels of several hormones, growth factors and cytokines, leading to decreased growth factor signaling, fewer vascular perturbations, and decreased inflammation. Together, these responses to calorie restriction result in decreased cancer risk and progression. An arrow preceding text denotes a directional effect (eg, activity or concentration). Abbreviations: IGF-1, insulin-like growth factor-1; ApN, adiponectin; PAI–1, plasminogen activator inhibitor–1; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator; VEGF, vascular endothelial growth factor; PI3K, phosphoinositide 3-kinase; mTOR, mammalian targt of rapamycin; NF-kB, nuclear factor kB; COX-2, cyclooxygenase-2.