Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. The prognosis for patients with ccRCC has improved over recent years with the use of combination therapies with an anti-programmed death-1 (PD-1) backbone. This has enhanced the quality of life and life expectancy of patients with this disease. Unfortunately, not all patients benefit; eventually, most patients will develop resistance to therapy and progress. Recent molecular, biochemical, and immunological research has extensively researched antiangiogenic and immune-based treatment resistance mechanisms. This analysis offers an overview of the principles underpinning the resistance pathways related to immune checkpoint inhibitors (ICIs). Additionally, novel approaches to overcome resistance that may be considered for the trial context are discussed.