VHL Alliance

This session brings together experts who discuss the latest advancements in diagnosing and treating VHL-related tumors. Dr. Shizou Mukai discusses retinal hemangioblastomas in VHL patients, stressing early eye exams and laser photocoagulation to prevent blindness; belzutifan’s eye benefits need more study. Dr. Prashant Chittiboina covers CNS hemangioblastomas, recommending surgery based on symptoms, as tumor growth is unpredictable and monitoring is vital. Dr. Alberto Feletti supports a “wait-and-see” approach for asymptomatic CNS tumors, with surgery or gamma knife reserved for symptomatic cases; belzutifan remains experimental. Dr. Naris Nilubol explains that pancreatic neuroendocrine tumors in VHL are often silent and best detected by advanced imaging; belzutifan can reduce surgical needs. Dr. Reut Halperin links VHL gene variants to higher risks of diabetes and stroke, suggesting carriers develop diabetes earlier than others. Regular cardiometabolic monitoring may improve outcomes for individuals with VHL mutations.

This session delves into innovative strategies for targeting VHL-related pathways and modeling VHL disease in a laboratory setting. Dr. Qing Zhang outlines four strategies to treat VHL-related kidney cancer: blocking HIF-2α or tyrosine kinases, targeting lipid metabolism, exploiting synthetic lethality, and using PROTACs to degrade key proteins. Dr. Ruhee Dere studies VHL and SETD2 loss on chromosome 3p, showing both regulate proper cell division; inhibiting Aurora kinase A may stop cancer cell replication. Dr. Sakari Vanharanta links VHL loss to chronic kidney injury repair pathways, explaining slow tumor development and organ-specific cancer risk. Dr. Giannicola Genovese finds metastatic kidney tumors depend on mitochondrial energy production, suggesting targeting mitochondria could stop aggressive growth. He also uses stem cell models to explore why some organs are cancer-prone. Dr. Ian Frew reveals KDM5C (X) and KDM5D (Y) have distinct roles, explaining sex-based differences in kidney cancer behavior and treatment response.

In this informative session, the speakers explore the molecular bases of Von Hippel-Lindau (VHL) disease, highlighting the influence specific genetic mutations can have on tumor growth. Dr. Tom Mitchell explains that tumor growth in VHL disease is unpredictable, with macrophages producing IL-1 beta promoting aggressive tumor behavior; blocking IL-1 beta may slow growth. Dr. Isaline Rowe finds that multiple kidney tumors in VHL patients behave differently, each showing variable 3p loss, suggesting independent development and variable drug response. Dr. Samra Turajlic studies tumor evolution, showing that VHL loss starts the process and additional chromosomal changes (like 9p, 14q loss) drive aggressiveness and metastasis. Francesca Cuomo examines gender differences in kidney cancer, noting that males are more affected due to loss of the X-linked KDM5C gene. Mouse studies show both sexes develop tumors when VHL, PBRM1, and KDM5C are lost, but females develop more. Her work suggests genetic and gender factors together shape tumor risk and treatment outcomes.