Identifying a novel role for the Von Hippel-Lindau protein in phosphoinositide metabolism and its potential as a personalized therapeutic strategy in renal cell carcinoma
Overview. There are 6,600 adults in Canada that will be diagnosed with kidney cancer in 2020. Renal Cell Carcinoma incidence has increased in the last 20 years particularly in developed countries. Unfortunately, these tumors are asymptomatic and 30% of patients present metastases at diagnosis. There is no curative treatment for metastatic RCC and it is crucial to develop new approaches to treat this disease. Research progress. We work on novel therapeutic strategies to treat RCC. Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is an early event reported in up to 90% of RCC. We previously identify STF-62247, a small molecule that specifically kills renal cancer cells with a loss of VHL. Our recent studies identified the lipid kinase Pikfyve as the target of STF-62247. Objectives. We hypothesize that genetic mutations that drive aggressive RCC can be targeted through lysosomal disruption. Our study aims are to demonstrate the potential of the PIKfyve complex as a therapeutic target for VHL-inactivated tumors and link specific mutations found in RCC to lysosome vulnerabilities. Outcomes. Our study aims to develop targeted therapies against RCC, the premise of which is based on our expertise in lysosome research.