Fig. 6

Possible mechanism of afatinib-TMZ combination therapy in GBM. TMZ targets the differentiated proliferating GBM cells but fails to eradicate slow-growing CSCs and result in tumor progression. Afatinib decreases proliferation of U87EGFRvIII cells by inhibiting EGFRvIII/AKT signaling, cell migration and invasion by inhibiting EGFRvIII/JAK2/STAT and FAK (Tyr-925) signaling pathways. Afatinib by inhibiting EGFRvIII-cMET cross-activation decreases CSC stemness possibly by downregulating stemness transcription factors Oct3/4 and Nanog. Dotted line indicates possible effects