Speakers - CRDWC 2025

Abstract

In February 2025, Belzutifan (Welireg®) has been approved in Europe as a new smart molecule for the treatment of advanced sporadic renal cell carcinomas of the clear cell type (ccRCC). This new drug is an inhibitor of hypoxia inducible factor 2 alpha (HIF-2-alpha). In the recent ten years Belzutifan has been identified by the elucidation of the complex interaction between HIF-2-alpha and the protein (p) of the von Hippel-Lindau (VHL) tumor suppressor gene. 100 years ago, the VHL syndrome has been defined as a hereditary tumor predisposition syndrome. Persons who have inherited a pathological variant of the VHL gene will develop a variety of different tumors from all three germ layers, including ccRCC. The VHL gene has been identified in 1991, and characterized as a small gene, evolutionary highly conserved with a large number of various functions. In 2019, the nobel prize has been awarded for the discovery of hypoxia-inducible factor as a key transcription factor interacting with pVHL that regulates gene expression in response to decreases in cellular oxygenation. The talk will present data on the characterization of VHL and outline the pros and cons, the chances and pit-falls of a commerce driven research. ROI in science is very different from ROI in finance. It will be shown that the insights achieved by the exact characterization of the molecular patho-mechanism in rare (inherited) diseases will become helpful to develop new treatments for more common sporadic counterparts of that particular tumor as seen here in sporadic ccRCC. Another lessons from the scientific experiences of the recent years, including the human genome project will be to understand the need to think beyond genomics in functional terms, and also including new approaches for clinical trials.