In 2022, there will be an estimated 81,180 new cases of bladder cancer in the United States, making it the 7th most common cancer, and will result in an estimated 17,100 deaths. In the last decade there have been some important advances in the treatment of bladder cancer, but the prognosis remains particularly poor for those who are found to have a tumor that cannot be surgically removed and for those whose cancer has spread to other parts of the body (metastatic disease). Our lab has been trying to understand why some patients don’t respond to certain treatments and also trying to determine if there are ways to improve responses to therapy. We have now found that in a specific subtype of bladder cancer there are higher levels of two proteins (FGFR3 and Nectin-4), both of which can be targeted by some of the newly approved drugs for bladder cancer. Additionally, we have found that by using a drug that halts the activity of FGFR3 we see the levels of the other protein, Nectin-4, go up. This is a potential sign that the two drugs may be synergistic in this subtype of bladder cancer. In our proposed research we first plan to try and understand more about why levels of Nectin-4 go up when we halt FGFR3 activity. This has the potential to reveal additional therapeutic targets in the treatment of bladder cancer. We then plan to study the combination of an FGFR3 inhibitor (a drug called erdafitinib) and a drug that targets Nectin-4 to see if this is an effective combination in treating bladder cancer. We will also evaluate this combination with immunotherapy, which is another newly approved and effective treatment for bladder cancer. This portion of the study will be carried out in mice. In addition to evaluating the effectiveness of these different regimens we will also monitor for safety. If we find that this new combination of drugs is effective in this subtype of bladder cancer it can have important implications for further investigation and treatment in patients.

Clark-Garvey, S., Zhou, M., Truong, A., Beckabir, W., Sturdivant, M., & Kim, W. (2023). Abstract 4867: Effect of FGFR3 activity on Nectin-4 expression in urothelial carcinoma. Cancer Research, 83(7_Supplement), 4867–4867. https://doi.org/10.1158/1538-7445.AM2023-4867

Pope Fellowship (UNC Institutional Grant)
Lineberger Comprehensive Cancer Center Development Award (UNC Institutional Grant)

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