Figure 9. Feedback loop in TKI therapy.
IL-6 and VEGF activate AKT-mTOR and the STAT3 signaling cascade, consequently leading to enhanced secretion of IL-6 and VEGF. Secreted IL-6 and VEGF can again re-activate tumor cells and thus trigger tumor progression. A combination therapy of TKI together with an anti-IL-6R antibody could inhibit this amplifier circle.