VHL and nonpapillary renal cell carcinoma: A dual-regulated Ad9xHRE1A virus, in which the essential viral E4 gene is driven by the E2F-1 promoter and the E1A gene is controlled by an artificial promoter containing nine tandem hypoxia-responsive elements (HREs) for HIF binding, achieved specific anti-tumor effects in VHL-deficient ccRCC (Cuevas et al., 2003).