Molecular Therapeutics of Kidney Cancer: MET Gene and BHD Gene

Division Of Basic Sciences - Nci

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Abstract

In 1994 we discovered hereditary papillary renal cell carcinoma. In 1997 We identified the MET gene as the gene for the inherited form of type 1 papillary kidney cancer associated with Hereditary Papillary Renal Carcinoma. Intense study of the MET gene pathway has provided the opportunity to develop agents targeting this pathway for patients with HPRC-associated kidney cancer as well as patients with sporadic, non-hereditary papillary kidney cancer. In 1999 we described that renal cell carcionoma is a part of Birt-Hogg-Dube syndrome. In 2002 we discovered the Birt Hogg Dube gene, FLCN. We have shown what the BHD gene is the cell's bioenergetic and nutrient sensor. Since then we have described the FLCN gene pathway and shown this is likely the reason why when you exercise you live longer, have less heart disease, less type 2 diabetes, less cognitive dysfunction and less cancer. This pathway is the scientific basis for these findings. Birt-Hogg-Dub syndrome is a hereditary cancer syndrome in which affected invidivuals are at risk for the development of cutaneous fiborfolliculoma, pulmonary cysts and chromophobe, hybrid/oncocytic and clear cell kidney cancer. The gene for Birt-Hogg-Dub syndrome is the BHD gene. We have found mutations in the BHD gene in ~95% of our BHD families. Studies are underway to determine how inactivation of the BHD gene can lead to kidney cancer and how we can target this pathway for treatment of BHD-associated kidney cancer as well as sporadic, non-inherited chromophobe kidney cancer.