The IR, IGF-1R and their hybrid receptors are expressed by most human tumors, whereby predominant expression of the IR-A isoform correlates with a poor differentiation grade.30 Among the pathways activated by IR and IGF-1R signaling are the RAS−RAF−MEK1/2−extracellular signal-regulated kinase (ERK)-1/2 pathway34 and the phosphatidylinositol-3-kinase (PI3K)−AKT−mammalian target of rapamycin (mTOR) pathway, two fundamental pathways for tumor cell proliferation and survival (Figure 2). Here, PIK3CA is linked to neoplasm.