In addition to the ability to transit into distinct CSC states with different competence to evade drug toxicity to disseminate to distant organs, cancer cell plasticity has been shown to be linked to the epithelial-to-mesenchymal transition-like program in melanoma that relies not only on cell-autonomous mechanisms but also on signals provided by the tumor microenvironment and/or signals induced in response to therapy [82,83] in response to active mutations in key molecules of both MAPK and PI3K/AKT/PTEN pathways [84,85]. Here, PIK3CA is linked to cancer.