Intrahepatic cholangiocarcinoma (ICC) is the second most common kind of liver cancer. It is a very difficult disease to treat. Only about one out of ten patients live more than five years after the cancer has been detected. There are several different types of ICC. One important type has changes in a gene called the Fibroblast Growth Factor Receptor 2 (FGFR2). Drugs that turn off FGFR2 cause the tumors to shrink, but the tumors eventually become resistant to the drug and begin to grow again. The goals of this project are to understand what causes drug resistance and to develop ways to prevent it from happening. In this project, we will study samples of tumors from patients who are being treated with drugs against FGFR2. We will also make models that allow us to study ICC in the laboratory. Finally, we will use a method that could allow us to create a new kind of drug that is better at turning off FGFR2. We hope that our work will result in new treatments that help patients with ICC to live longer.