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Figure 3. EGFR/PI3K/MAPK/ERK1/2-FOXO3a pathways in cancer drug resistance. Overexpression of MIEN1 and ABCG2/ABCB1 initiates the cisplatin resistance by targeting Akt/RelA/p50 and efflux of cisplatin respectively. MIEN1 targets Akt/RelA/p50 and induces overexpression of the anti-apoptotic proteins. Akt protein activated by MIEN1 inhibits FOXO3a function. Together, P38 and JNK phosphorylate FOXO3a protein which results in to its ubiquitination and proteasomal degradation. MEK/ERK pathway phosphorylates FOXM1 proteins which results in to translocation of these proteins inside the nucleus. Phosphorylated FOXM1 transcribes several genes which positively involves in drug resistance