A Review: Novel Therapies for Advanced Clear Cell Renal Cell Carcinoma

The therapeutic landscape of clear cell renal cell carcinoma (ccRCC) has dramatically evolved in the last decade. Immuno-oncology (IO) and/or tyrosine kinase inhibitor (TKI) based doublet therapies have become standard in the frontline setting for most patients with advanced ccRCC. For previously-treated advanced ccRCC, multiple agents are available including belzutifan, a hypoxia inducible factor 2 alpha (HIF2-α) inhibitor. However, the challenging goal of developing therapies with a unique mechanism of action remains. Many such promising agents are currently in development such as novel TKIs, inhibitors targeting alternative checkpoints, cellular therapies, radioligands, antibody-drug conjugates, and agents targeting fatty acid metabolism. Further, the role of microbiome is being actively investigated in advanced ccRCC, with ongoing studies evaluating its effect when combined with standard therapies. Mature data from trials with these agents is eagerly awaited.