VHL and nonpapillary renal cell carcinoma: In that context, PI3K inhibitor TGX221 has been shown to inhibit the growth of RCC cell lines containing VHL and SETD2 mutations suggesting that VHL/HIF and PI3K/AKT pathways may have a role in the deregulation of chromatin remodeling and CIN, involved with the pathogenesis of ccRCC (32).