von Hippel-Lindau disease: recent advances and therapeutic perspectives.
von Hippel-Lindau disease is a hereditary cancer syndrome predisposing carriers to the development of a panel of highly vascularized tumors such as central nervous system and retinal hemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas, pheochromocytomas and pancreatic neuroendocrine tumors. The disease is the foremost cause of inherited renal cell carcinomas, which is induced by germline mutations of the VHL tumor-suppressor gene also inactivated in most sporadic renal cell carcinomas. VHL appears to be a pivotal gene in the oxygen-sensing pathway, mainly involved in targeting the hypoxia-inducible factors for ubiquitination. This discovery is opening the way for the development of new specific drugs inhibiting hypoxia-inducible factors and/or their downstream targets, possibly representing an attractive treatment not only for von Hippel-Lindau disease but also for sporadic renal cell carcinomas and others cancers.
Génétique Oncologique EPHE, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France. stephane.richard@kb.u-psud.fr
Stéphane
S
Richard
D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000628:therapy*