Figure 1. The discovery of the VHL/EglN/HIF pathway as a central mediator of hypoxia signaling has paved the way for introduction of drugs that modulate the pathway for the treatment of human disease.

Because the pathway is so central to so many pathological conditions, pharmacologics are being used for the treatment of cancer, as well as being tested for other conditions, such as anemia and cardiovascular and pulmonary diseases. Therapeutics targeting this pathway include VEGF pathway inhibitors (bevacizumab, sorafenib, sunitinib, pazopanib, axitinib, cabozantinib, and lenvatinib), mTOR inhibitors (temsirolimus and everolimus), EglN inhibitors in phase III trials (daprodustat, molidustat, roxadustat, and vadadustat), and investigational HIF-2α inhibitors (PT2385, PT2977, and RNAi [phase I]).