Centre for Inflammation Research

Promising new target for the treatment of bile duct cancer

November 2020: New research suggests that disruption of a chemical messenger TWEAK could disrupt the growth of an aggressive form of liver cancer and improve the effectiveness of current treatments for the disease.

Human bile duct cancer containing tumour cells, cancer associated fibroblasts, and Fn14 receptors
Human bile duct cancer containing tumour cells, cancer associated fibroblasts, and Fn14 receptors (Image credit: Dwyer et al.)

Cholangiocarcinoma or bile duct cancer is resistant to chemotherapy and has a high recurrence following surgery, with less than 25% of patients surviving more than 5 years.

In Cholangiocarcinoma, tumour growth is driven by interactions between tumour cells and other cells that form a supportive environment. 

A chemical messenger TWEAK, produced by immune cells (macrophages), alters the natural immune response and increases the growth of the cancer.

TWEAK works through its receptor (Fn14) found on tumour cells and cancer associated fibroblasts. It alters the type of immune cells in the tumour and increases cancer associated fibroblast growth.

The study team, including Dr Tim Kendall and Professor Steve Wigmore from CIR, found increased levels of Fn14 in both 174 human cholangiocarcinoma samples and rat and mouse models of the disease.     

Results obtained from a mouse with the Fn14 gene deleted and mice dosed with an antibody that inhibits the effects of TWEAK both indicate that the TWEAK pathway shows promise as a target for future therapies.

Professor Stuart Forbes, Director of CRM and CIR-affiliated researcher who co-led the study team said,

We have found that the environment surrounding the cancer is very important in driving its growth. We are excited by this finding because it offers a new target for treatment of this aggressive and life limiting cancer

Helen Morement, CEO of AMMF - The Cholangiocarcinoma Charity said, 

This is potentially very exciting. With increasing incidence globally, mortality that mirrors that incidence and no improvement in survival for decades, cholangiocarcinoma is an under-researched, much neglected, truly devastating disease.

We are delighted, therefore, to have been able to support the dedicated team in Edinburgh in this work on cholangiocarcinoma and hope that the results of their research will prove to be a real step forward in not only understanding this cancer, but also towards some long awaited possible improvements in treatment.

The study was conducted by Dr Benjamin Dwyer and colleagues in collaboration with co-senior author, Associate Professor Nina Tirnitz-Parker, of Curtin University in Perth, Australia with support from the National Health and Medical Research Council, Australia. This work was co-funded by AMMF - The Cholangiocarcinoma Charity and published in Journal of Hepatology.

Journal of Hepatology article (Dwyer et al, 2020)

AMMF – The Cholangiocarcinoma Charity

Curtin University, Perth, Australia