Clinical Studies of the Molecular Genetic Basis of Kidney Cancer

$1,476,414ZIAFY2025CANIH

Division Of Basic Sciences - Nci

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Abstract

When we started our work in kidney cancer, kidney cancer was a single disease. We now know that kidney is not a single disease, it is made up of a number of diseases, with different clinical courses, responding differently to therapies and caused by different genes, each with a different clinical course and responding differently to therapy. Over the past 43 years we have discovered 10 different kidney cancer genes and discovered 9 different diseases! We have described precision surgeries in patients with VHL -/- clear cell RCC, Met-mutant type 1 papillary RCC, FLCN -/- chromophobe RCC, TFE3 RCC, FH -/- RCC and SDH -/- RCC. Our work on discovery of the VHL gene and its pathway have led to the FDA approval of 11 drugs that target the VHL pathway. Our work on FH -/- RCC, for which there was no effective form of therapy, has led to our recent New England Journal of Medicine publication of bevacizumab and erlotinib in which we find 72 % response! We have shown that TFE3/B is the critical target for 7 different types of genetically defined kidney cancer and we are currently working on therapy for these forms of RCC.

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