Using both monolayer cell cultures, tumor cells grown as spheroids as well as organotypic short-term cultures of renal tumor tissue slices, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for the use of ATM inhibitors in combination with CX-4945 in ccRCC. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.