Starvation, Stress Resistance, and Cancer

• Published in: Trends in endocrinology and metabolism 2018-04, Vol.29 (4), p.271-280
• Main Authors: Buono, Roberta, Longo, Valter D.
• Format: Article
• Language: English
• Subjects: cancer; differential stress resistance; differential stress sensitization; fasting-mimicking diet; IGF-1; starvation
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2018.01.008

Cancer cells are characterized by dysregulation in signal transduction and metabolic pathways leading to increased glucose uptake, altered mitochondrial function, and the evasion of antigrowth signals. Fasting and fasting-mimicking diets (FMDs) provide a particularly promising intervention to promote differential effects in normal and malignant cells. These effects are caused in part by the reduction in IGF-1, insulin, and glucose and the increase in IGFBP1 and ketone bodies, which generate conditions that force cancer cells to rely more on metabolites and factors that are limited in the blood, thus resulting in cell death. Here we discuss the cellular and animal experiments demonstrating the differential effects of fasting on normal and cancer cells and the mechanisms responsible for these effects. Dysregulated metabolism is one of the emerging hallmarks of cancer cells. Differential stress resistance (DSR) and differential stress sensitization (DSS) responses are the mechanisms caused by fasting and fasting-mimicking diet (FMDs) to promote protection of normal cells and induce cancer cell death. Fasting-dependent reduction in glucose and IGF-1 mediates part of the DSR and DSS effects. Fasting and FMDs have the potential for applications in both cancer prevention and treatment.