EPAS1 and nonpapillary renal cell carcinoma: Camptothecin (CPT) and its analogs, topotecan and irinotecan, are topoisomerase I inhibitors that prevent topoisomerase I-mediated unwinding and DNA repair, leading to accumulation of DNA double-stranded breaks and cell death.15 These agents are also potent inhibitors of HIF-1α and have been studied extensively for HIF-1α-targeted therapy.16, 17, 18, 19, 20, 21 CPT-based nanopharmaceuticals are currently in clinical trials for advanced kidney cancer; however, to our knowledge, no reports exist as to the effects of CPT on HIF-2α function in ccRCC.