Investigating the function of FZD7 in cholangiocarcinoma and determining the therapeutic benefit of targeting FZD7 with a novel FZD7-ADC

Cholangiocarcinoma (bile duct cancer) is the second most common liver cancer globally, with incidence rising, including in younger age groups. Difficulties in diagnosing early means 75-85% of cholangiocarcinoma patients are diagnosed when their cancer has spread and surgery may not be an option. Survival rates for cholangiocarcinoma are amongst the worst of all cancers and therefore new treatments are urgently needed.

A receptor protein, FZD7, which is active in cholangiocarcinoma, is known to have a role in the growth and spread of cancer. We are proposing to test a new drug called FZD7-ADC which binds to FZD7. FZD7-ADC is able to shrink ovarian tumours, but we do not know if it is effective in cholangiocarcinoma.

Cholangiocarcinoma can spread from the bile duct to other sites including the lungs, peritoneum (the lining of the abdominal cavity), or different areas of the liver. It is not understood whether the FZD7 receptor encourages growth of the cholangiocarcinoma cells when they arrive at these new sites. Therefore, this project will also investigate how FZD7 transmits signals between the cholangiocarcinoma cells and the lung/liver/peritoneum. We shall then test which genes FZD7 is activating to make cholangiocarcinoma cells grow. This will provide new robust targets for future cholangiocarcinoma therapy.