The Nobel Prize in Physiology or Medicine 2019 was awarded to three distinctive doctors, William G. Kaelin Jr, Peter J. Ratcliffe and Gregg L. Semenza. They discovered how cells could sense and adapt to hypoxic conditions. Importantly, their findings directly contributed to the drug development of HIF-PH inhibitors and HIF-2 alpha inhibitors for the treatment of renal anemia and kidney cancer, respectively.
The field of study of hypoxia has begun in 1993 when VHL gene was identified as a cause of von-Hippel Lindau (VHL) disease. VHL patients harbored germline mutation of this gene and develop hypervascular tumors such as kidney cancer and retinal hemangioma. It was revealed that the VHL gene product played major roles as E3 ligase and regulated hypoxia inducible factor (HIF) alpha in protein level. HIF is a transcriptional factor that controls thousands of genes required for cells to adapt hypoxic conditions such as VEGF. Moreover, HIF-2 was proved to be a driver of kidney cancer.
Based on these, HIF-PH inhibitors was developed to prevent HIF alpha from the degradation and induce EPO under normoxia to treat renal anemia. On the contrary, HIF-2 alpha inhibitor successfully downregulated HIF-2 target genes and repressed tumor progression of kidney cancer in VHL patients.  
I was fortunate to participate in Dr. Kaelin`s laboratory and learn the importance of translational research in the novel drug development. I will present how the research group could overcome “Valley of death” and finally achieve the Proof of Concept required for first-in-human clinical trials.