The retrospective analysis of tumor molecular data from the phase III JAVELIN Renal 101 trial25 of frontline avelumab plus axitinib compared to sunitinib in patients with advanced renal cell carcinoma challenged the standard biomarkers used to predict therapy.18 Hence, neither tumor mutational burden nor programmed cell death ligand 1 (PD-L1) levels but instead newly identified immunomodulatory and angiogenesis GES appeared to define progression-free survival. This evidence concerns the gene CD274 and hereditary clear cell renal cell carcinoma.