Fig. 1

Key findings from existing tumor models on the correlation between nutrients, stress response, and cancer. Schematics of the interconnecting feedback loops between nutrient levels and stress response. Step 1: The cascade of kinase action. Fasting triggers elevated levels of glucagon (Gluc) and epinephrine (EPI), which in turn induces a cascade of cyclic adenosine monophosphate (cAMP)-dependent signaling via adenylate cyclase (AC). This reaction then leads to the activation of protein kinase A (PKA) and glycogen phosphorylase, which promotes glycogenolysis. Step 2: Process of gluconeogenesis. Amino acids (AA), lactate, and glycerol (Gly) are substrates of gluconeogenesis [36] and glycerol-phosphoric acid (GAP), and phosphoenolpyruvate acid (PEP) are intermediates of the reaction. In addition to the involvement of certain key enzymes such as pyruvate carboxylase, transcription factors such as cAMP response element-binding protein (CREB) are also involved in the process of gluconeogenesis [35]. Step 3: The onset of DSR - Under fasting conditions, Gluc and EPI initiate the cascade of kinase action that releases glucose from the stored glycogen via the process of glycogenolysis [34]. CREB is critical in coordinating the fasting-mediated activation of gluconeogenesis in the liver [34]. The extreme changes caused by fasting include reduction of IGF-I and glucose (GLU) and an increase in IGFBP