Figure 1.

Timeline of US Food and Drug Administration drug approvals for advanced-stage renal cell carcinoma. Initial clinical success was seen with targeted therapies affecting angiogenesis and PI3K pathways in 2005, until 2015 when the first immune checkpoint inhibitor was approved for use. Within the last five years, more successes have been experienced with combination therapies, suggesting therapeutic synergy. Belzutifan is only approved for von Hippel–Lindau-related clear-cell renal cell carcinomas. Abbreviations: IFN-α = interferon alpha; TKI = tyrosine kinase inhibitor; mTOR = mammalian target of rapamycin; VEGF = vascular endothelial growth factor; HIF-2α = hypoxia-inducible factor-2α.