This PI3K-AKT-dependent adaptive response to BRAFi, along with the high frequency of melanomas with loss of function of PTEN [14-16] and other alterations linked to this pathway [12,29,32,49], indicate that the addition of a PI3K/AKT inhibitor to MAPK inhibitors may be necessary to obtain a long-term clinical benefit. Here, PIK3CA is linked to melanoma.