The Target Area of Belzutifan in Towards Clear Cell Renal Cell Carcinoma (ccRCC)

As a kidney cancer patient,clear cell renal cell carcinoma (ccRCC) is notably aggressive, often because of poor outcomes due to late diagnosis and treatment resistance. However, current therapies are so limited. The clinical research reports that when people are treated with these current therapies, they show high blood pressure and their hands and feet are easily hurt. Also, patients have gastrointestinal discomfort. All these reported side effects reduce patient compliance. Furthermore, these treatments are not curative and are challenged by the high degree of tumor heterogeneity. As a result, developing new therapeutic strategies for ccRCC is an urgent requirement. The VHL gene is essential for the degradation of hypoxia-inducible factor 2-alpha (HIF-2). While the pathogenesis of ccRCC is primarily driven by the mutation or loss of the VHL gene. As a result, loss of function of the VHL gene leads to the accumulation of the key transcription factor HIF-2. Targeting this pathway offers a promising tumor-specific approach with high therapeutic feasibility. Belzutifan is a novel drug that directly inhibits the HIF-2/ARNT complex, thereby downregulating genes essential for tumor metabolism and angiogenesis. This review explores the evolving landscape of ccRCC treatment, highlighting the mechanistic rationale and clinical performance of HIF-2 inhibitors in combination regimens.