Here, we connect dysregulated signaling in the MAPK and PI3K/PDK1/AKT/mTOR (where PDK1, phosphoinositide-dependent protein kinase 1; mTOR, mammalian target of rapamycin) pathways with dysregulated cell cycle subverting normal cell proliferation and differentiation, resulting in NDDs or cancer. This evidence concerns the gene PIK3CA and cancer.