PTEN and melanoma: In a separate study, the same group demonstrated that the combined blocking of PI3K and BRAFV600E significantly increased the durability of therapy responsiveness to an MEK1/2 inhibitor (GDC-0973) in BRAFV600E/PIK3CAH1047R or BRAFV600E/PTENNull melanoma, suggesting that combined PI3K-mediated therapeutic intervention (with BRAFi) will be helpful in patients, whereas PTEN silencing and PIK3CAH1047R mutations are responsible for PI3K activation [94].