Overview of clear cell renal cell carcinoma: from mechanisms to clinical

Clear cell renal cell carcinoma is the most common histological subtype of kidney cancer. Its development is often associated with mutations in the VHL gene, whose inactivation leads to the accumulation of HIF-2α. This accumulation of HIF-2α activates multiple signaling pathways, thereby promoting tumor growth and proliferation. Treatment strategies include surgical resection, targeted drugs, and immune checkpoint inhibitors. Previous targeted treatments were predominantly tyrosine kinase inhibitors. In recent years, the HIF-2α inhibitor, Belzutifan, has been approved by the FDA for the treatment of clear cell renal cell carcinoma. Its approval is due to its specific blocking of the HIF-2α signaling pathway and its ability to inhibit tumor growth. This article focuses on the pathogenesis, diagnosis, and treatment of clear cell renal cell carcinoma, with an emphasis on the clinical trial results of Belzutifan.