Jonathan Chou, MD, PhD

Bladder cancer is the 5th most common cancer in the United States and causes about 17,000 deaths each year. When it spreads to other parts of the body, patients usually live less than two years. In the past few years, a new type of treatment called antibody drug conjugates (ADCs) has changed how bladder cancer is treated. One of these drugs, enfortumab vedotin (EV), targets a protein on bladder cancer cells called NECTIN4. When EV is used alone or with immunotherapy, this new therapy can shrink tumors in nearly 70% of patients at first. Sadly, most patients with bladder cancer become resistant after about a year, which means that the cancer stops responding to the treatment.We first thought this resistance might happen because tumors lose expression of the target NECTIN4. But when we looked at tissue samples from patients whose cancer stopped responding, we found most resistant tumors still had it. This project will explore other reasons why resistance happens and how to delay or reverse it. This includes looking at how the drug is processed inside cells, how it gets broken down, and how immune cells around the tumor may play a role. We will study both cancer cells and patient samples to see what changes occur as resistance develops. We will also test new drug designs, try other ways of targeting NECTIN4, and build new lab models from patients whose cancers are resistant. This work could lead to better treatments not only for bladder cancer but also for other cancers treated with ADCs.