Figure 9. Chemotherapy induces the catabolic tumour stroma phenotype, which in turn activates antioxidant response, immune response and stemness in cancer cells.

A. Chemotherapy-induced DNA damage generate activation of HIF1, NFkB, TGFβ, STAT3 and JNK/AP1 signalling pathways in stromal cells, which stimulates their differentiation into CAFs, a switch to aerobic glycolysis and mitochondrial dysfunction, autophagy and senescence, release of inflammation cytokines and inhibition of interferon-mediated signalling. B. In contact with these catabolic fibroblasts, cancer cells react to chemotherapy by activating antioxidant and immune response signalling, and by activating stemness.