The current, updated ESMO guidelines for treatment of advanced/metastatic RCC indicate that: the combination of pembrolizumab and axitinib should be considered as a front-line therapeutic option for patients with advanced disease, irrespective of prognostic groups and of the PD-L1 biomarker status; the combination nivolumab and ipilimumab should be considered in patients with intermediate/poor risk status; VEGF-targeted therapy is recommended for those patients where pembrolizumab/axitinib or nivolumab/ipilimumab are not available or contraindicated. The gene discussed is CD274; the disease is renal cell carcinoma.