Fig. 6.

A model for fasting-dependent sensitization of tumor cells to chemotherapy. In response to fasting, glucose, IGF-1, and other pro-growth proteins/factors (including oncogenes) are reduced in the serum. Malignant cells respond to this reduction by activating Akt/S6K. Notably, S6K can also be activated independently of Akt via energy-sensing pathways such as AMPK-mTORC1 (34). These changes lead to an increase in oxidative stress, an increase in DNA damage, activation of caspase-3, and eventually cell death, particularly in the presence of chemotherapy.