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]. This evidence concerns the gene IGFBP3 and non-small cell lung carcinoma.