EGFR and ovarian carcinoma: We further observed a dose-dependent increase in p-ERK, p-90RSK and p-Akt by up to 2- to threefold in fentanyl-treated ovarian cancer cells (Fig. 5A and C, Table S5, p < 0.001), suggesting the activation of MEK/ERK and PI3K/Akt which are the major downstream signaling pathways of EGFR [20].