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Dr. Srinivas Viswanathan received a 2022 KCA Trailblazer Award for his research on “Advancing a Cell Surface Therapeutic Target in Translocation Renal Cell Carcinoma. Dr. Viswanathan is a medical oncologist at the Dana-Farber Cancer Institute. We spoke with Dr. Viswanathan about his work and the impact it can have on people with kidney cancer.

Can you summarize your research study?

Translocation renal cell carcinoma (tRCC) is a rare but aggressive subtype of kidney cancer that makes up about 5% of kidney cancers in adults and up to 50% of kidney cancer in children. tRCC has a distinct demographic in that patients tend to be female, younger, and present with more advanced disease than do patients with other subtypes of kidney cancer. Prognosis for tRCC subtype is poor, tRCC responds poorly to therapies that are effective in clear cell RCC – such as immunotherapies – and no molecularly targeted treatment for tRCC currently exists. A fundamental barrier to developing therapies is an incomplete molecular understanding of tRCC and how it differs from other kidney cancers. In this project, we will focus on identifying molecules that are located specifically on the surface of tRCC cells. This will allow us to ultimately develop drugs against these molecules, which would allow us to specifically treat tRCC.

Why are you interested in tRCC as a research subject?

tRCC is driven by a unique biology as compared with other subtypes of kidney cancer. Currently, the therapies that we have for tRCC are inadequate, and it therefore represents a major unmet need in kidney cancer research. Hopefully, a better understanding of the biological pathways that drive tRCC can lead to more effective therapies for this cancer in the future.

How are most people with tRCC treated today?

Unfortunately, currently available treatments are not targeted to the specific biology of tRCC. As a result, most patients with tRCC today are treated with agents that were originally developed for and tested in more common subtypes of RCC (e.g. clear cell RCC). While some of these drugs may have activity in tRCC, the ideal option would be to develop or repurpose therapies that are specifically tailored to tRCC. However, in order for such therapies to be identified, we first need to considerably advance our molecular understanding of the pathways that drive tRCC.

This research is pre-clinical but what would you want someone with tRCC now to know?

Research in this area is developing rapidly and we are constantly learning more about the biology of tRCC in the laboratory. In the short-term, I hope that we will be able to identify existing therapies that have already been tested in other kidney cancers or in other cancers, and that may have promising activity in tRCC. In the long-term, I hope that we will be able to identify novel therapeutic targets in tRCC that will enable the development of highly effective therapeutic agents specifically for this cancer type.

Do you have any guesses as to what kinds of therapies (IO, TKI, VEGF, other) might be effective in tRCC in the future? Do they already exist or would it be entirely novel therapies for a novel target?

Existing therapies for kidney cancer may be effective in some patients with tRCC. However, because this subtype of kidney cancer is rare, we have limited data to say whether one type of existing therapy may work significantly better or worse than another. We also need to be able to more accurately determine which patients will respond to which therapies.

It is certainly possible that therapies developed for other cancers or other diseases may have activity in tRCC, and identifying/repurposing such therapies is one area of research interest in our laboratory. However, in the long term, novel targets/therapies that are specific to tRCC may be the most promising option, given that the biology of tRCC is quite distinct from other RCCs.

What motivates you?

I am motivated by cancer research at the interface of discovery biology and clinical translation – uncovering the details of molecular pathways that can be developed into new therapeutics that ultimately improve and extend the lives of patients with kidney cancer.

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