Given the fact that over 80% of tumors from patients with advanced ccRCC express both HIF-1α and -2α [11,12], and with the knowledge that stable expression of HIFs is regulated by the rate of synthesis and degradation, it is expected that the combination of topotecan’s dose-sufficient inhibition of HIFS synthesis with SLM that targets HIFs degradation will result in a more selective and efficacious treatment modality. Here, HIF1A is linked to nonpapillary renal cell carcinoma.