The development of new forms of treatment of advanced renal cell carcinoma over the past two decades has been primarily focused on targeting the VHL/HIF pathway.
In recent years, functional characterization of the von Hippel-Lindau tumor suppressor, hypoxia-induced factors, and one of their key downstream effectors, the vascular endothelial growth factor (VEGF), has revolutionized treatment of advanced renal cell carcinoma.
In this review, the authors trace this illuminating tale, from the cloning of the VHL gene, to elucidating its biologic function, to the development of novel therapeutics that have dramatically changed the paradigm of managing advanced renal cell carcinoma.
The treatment of advanced renal cell carcinoma (RCC) has evolved significantly following the identification of the von Hippel-Lindau (VHL) gene and the function of its protein, and subsequent development of antiangiogenic therapies.