The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is one of the most extensively studied and has been demonstrated to be a critical mechanism of drug resistance induced by OPN in cancer cells, e.g., NSCLC cells show less sensitivity to DDP, due to overexpression of OPN, and the OPN-induced drug resistance may be mediated by activation of the PI3K/ extracellular signal-regulated kinases (ERK) pathway [72]. This evidence concerns the gene SPP1 and cancer.