Strikingly, as shown in Figure 4C, the capacity of KU-60019 alone or in combination with CX-4945 to induce cell death in these MCTS was impeded in an on-target manner by CAS9-mediated loss of HIF-2α, suggesting that the vulnerability to combined inhibition of ATM and CK2 in VHL-deficient ccRCC is positively correlated with HIF-2α expression levels. This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.