SDHB Pheo Para Coalition Research Project update: To establish a cell-based model for the discovery of new molecules that inhibit the degradation of altered SDHB and rescue its tumor suppressor function in PPGL
Summary:
In our SDHB Pheo Para Coalition funded project, we aim to examine whether we can artificially stabilize pathogenic Succinate Dehydrogenase subunit B (SDHB), a tumor suppressor gene. Pheochromocytomas and Paragangliomas (PPGL) patients harboring a pathogenic mutation in the Succinate Dehydrogenase subunit B (SDHB) experience increased cancer metastasis and limited treatment options. This is because SDHB pathogenic variants are rapidly degraded in PPGL, which inhibits its ability to carry out is usual tumor suppressor function.
With the generous support of a seed fund from the SDHB Pheo Para Coalition, we have made great progress on this project over the last 5 months. We have been able to establish succinate dehydrogenase (SDHB) deficient pheochromocytoma cell models in our lab for the first time. We are now investigating genetic methods to artificially stabilize the altered forms of SDHB that are known to cause various forms of hereditary pheochromocytomas and paragangliomas. This will allow us to examine the changes in SDHB function upon forcing higher levels of altered SDHB protein expression that are normally rapidly broken down in the cancer. Our hypothesis is that this will rescue their normal function and halt the initiation and/or progression of the cancer. We thank the SDHB coalition for their support thus far and look forward to continuing our work together.