Approximately 6,000 Texans will be diagnosed with kidney cancer each year. Tragically, more than 1,300 will succumb to the disease. Sarcomatoid renal cell carcinoma (sRCC) is the most aggressive type of kidney cancer with the worst prognosis. There are currently no effective treatments for this disease. sRCC has always been considered a "terminal stage" of RCC meaning that it represents tumors that have acquired multiple mutations and therefore no longer look anything like a kidney.

We recently found that mutation of only two genes is sufficient to cause metastatic sRCC in mice. When we compared the molecular characteristics of the mouse tumors to hundreds of human RCC tumors, we found that ...

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Approximately 6,000 Texans will be diagnosed with kidney cancer each year. Tragically, more than 1,300 will succumb to the disease. Sarcomatoid renal cell carcinoma (sRCC) is the most aggressive type of kidney cancer with the worst prognosis. There are currently no effective treatments for this disease. sRCC has always been considered a "terminal stage" of RCC meaning that it represents tumors that have acquired multiple mutations and therefore no longer look anything like a kidney.

We recently found that mutation of only two genes is sufficient to cause metastatic sRCC in mice. When we compared the molecular characteristics of the mouse tumors to hundreds of human RCC tumors, we found that our mice closely matched a small, previously un-noticed subset of RCCs. We believe that our data support the conclusion that sRCC represents its own unique and distinct class of human RCC. We will now use our mice as well as abundant sequencing data from human RCCs to develop ways to quickly and easily identify this new class of RCC (new diagnostics) as well as to identify potential therapies (candidate drugs can be rapidly and easily tested in mice prior to going to the effort and cost of human clinical trials). Finally, we will use the mouse model to understand the difference between sRCC and other types of RCC and why sRCC is so aggressive. We will focus on a specific protein, Serum response factor or Srf, that appears to be overactive in sRCC. We believe that inappropriate activation of Srf turns standard RCCs into sRCCs. If this is the case, there are therapeutic avenues we can pursue to prevent sRCC from forming in the first place.

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