Silencing of IGFBP-3 expression by promoter hypermethylation in cisplatin-treated tumor cells was reported previously to activate the PI3K/AKT pathway via de-repression of IGF-1R signaling, decreasing tumor cell sensitivity to cisplatin in NSCLC and inducing cisplatin-resistance in NSCLC patients [91]. Here, AKT1 is linked to neoplasm.