Fig. 2

The mechanisms by which autophagy modulation affects chemosensitivity are multifaceted and involve multiple signaling pathways. The PI3K/Akt/mTOR pathway suppresses autophagy, while PTEN activation, as well as CaMKKβ, ATM or LKB1-mediated AMPK activation, can promote autophagy by activating the ULK1/2 complex or deactivating mTOR. Autophagy is also induced by Src/STAT3 signaling pathway through HO-1 activation and the ERK/JNK signaling pathway activated by HMGB1. Additionally, ROS stimulates autophagy by inhibiting JAK2/STAT3 and p38/mTOR pathways, while the IL-6/STAT3 pathway activates ERK and induces autophagy by repressing ERS. These signaling pathways further regulate the sensitivity of tumor cells to chemotherapy through the activation or hyperactivation of autophagy