PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. PIK3CA mutations are present in ~5% of cutaneous melanomas. PIK3CA M1043I is a known oncogenic hotspot mutation. M1043I confers a gain of function on the protein as indicated by in increased activation of downstream signaling and and transformation in cell culture. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.