fig7

Figure 7. An overview of the PI3K/Akt/mTOR pathway and its role in overcoming drug resistance mediated by sesquiterpene lactones. This pathway is activated by cell surface receptors, including RTKs and GPCRs, leading to PI3K activation and the generation of PIP3. PIP3 facilitates the phosphorylation of Akt and promotes the membrane translocation of both Akt and PDK1, triggering downstream signaling through mTOR. This activation enhances drug resistance by upregulating ABC transporter expression, thereby increasing drug efflux. Moreover, the PI3K/Akt/mTOR pathway regulates key processes such as autophagy and tumor proliferation through mTOR modulation. Its interaction with the TRAIL pathway further amplifies the complexity of drug resistance networks by influencing apoptosis, reinforcing the role of this pathway in resistance mechanisms. PI3K: Phosphoinositide 3-kinase; RTKs: receptor tyrosine kinases; GPCRs: G protein-coupled receptors; PIP3: phosphatidylinositol 3,4,5-triphosphate; PDK1: phosphoinositide-dependent kinase-1; ABC: ATP-binding cassette; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand.