Written By: Zeynep Kahramanoğlu

To highlight Gallbladder/Bile Duct Cancer Awareness Month, the RIOT team is shedding light on a group of rare cancers called biliary tract cancers.

The biliary tract, or biliary system, involves the production, transportation, storage, and secretion of bile through the gallbladder and bile ducts. The main function of bile is to help digestion and drain waste products from the liver into your intestines.

Biliary tract cancers, including gallbladder and bile duct (also known as cholangiocarcinoma) cancers, are rare and prognosis for these diseases are poor. According to the Canadian Cancer Society, the 5-year net survival rate for people diagnosed with gallbladder cancer is at only 19% and for people diagnosed with localized (Stage 1) bile duct cancer, the relative survival rate is at 30%. Unfortunately, when the disease has spread to other areas of the body, the relative survival rate decreases significantly, to a rate of only 2%. The spreading to other areas of the body is known as advanced bile duct cancer. When these diseases are found at advanced stages, they are more difficult to treat.

The optimal approach to treat biliary cancers are through surgery, radiation therapy or chemotherapy. Typically, the best outcomes for patients is achieved through management by multidisciplinary teams, which include many types of healthcare professionals. Thanks to research, there are many new, innovative treatments that can help improve the lives of people living with biliary tract cancers.

What’s New in Treatment

For gallbladder cancer, two immunotherapy drugs called pembrolizumab and nivolumab are approved by Health Canada. Immunotherapy helps our immune system better target and kill cancer cells. Both drugs are used for microsatellite instability-high gallbladder tumours or MSI-H tumours. MSI is an indication that the cell has a defect in its ability to repair damaged DNA, which leads to more genetic mutations. This highlights how stable our DNA is. The immunotherapy drugs have shown to be effective in this group of patients with MSI-H gallbladder tumours.

In bile duct cancers, there are targeted treatments that identify and attack a specific mutation in the cancerous bile duct cells. One of those targeted treatments is called pemigatinib, which has been shown to be effective, but unfortunately, is not available for Canadian patients. The Canadian Agency for Drug and Technology in Health has recently made the decision to reject the submission to publicly fund the drug. In the U.S. and the U.K., as well as other countries in Europe, this drug helps patients who can’t have surgery and have advanced bile duct cancer with a FGFR2 fusion gene. A fusion gene is when two separate genes have joined together and as a result, creates a protein that does not function properly. The drug targets the malfunctioning FGFR2 protein, slowing down the growth of cancer cells.

The FDA has also approved a drug called ivosidenib, which targets bile duct cancers with a mutation in the IDH1 gene. This mutation causes cancer cells to grow, so blocking it effectively slows down disease progression. Last year, the FDA also approved dabrafenib in combination with trametinib for biliary tract cancer patients. Dabrafenib targets a mutation in a gene called BRAF, while trametinib targets a protein called MEK.

Harnessing the Power of the Immune System

Last year, a large clinical trial called TOPAZ-1 began to offer hope for people with rare, aggressive biliary tract cancers. Led by Dr. Do-Youn Oh from Seoul National University Hospital in South Korea, this first-of-its-kind study explored a new immunotherapy drug (called durvalumab) which was used in addition to standard chemotherapy. The study showed that the combination can modestly extend how long people with advanced biliary tract cancer lived, without causing additional serious side effects. This study included 685 patients and was conducted across 18 countries.

The drug works by blocking a specific immune checkpoint. An immune checkpoint acts like a gatekeeper of immune response, keeping the immune responses in check. A hallmark of cancer is its ability to trick and escape the immune system, turning the immune response “off” through the immune checkpoint. The drug blocks the immune checkpoint and prevents the “off” signal from being sent, allowing the immune cells to kill cancer cells.

Research on biliary tract cancers has come a long way, with improvement to current treatment strategies and emergence of new immunotherapy drugs to help patients live longer. There is still much more to do. Research continues to move forward and explore new ways to improve outcomes for patients.

    Want to learn more? Read more here:

    Cancer Net: Bile Duct Cancer Types of Treatment

    Cancer Net: Gallbladder Cancer Types of Treatment  

    TOPAZ-1 Trial Paper: Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer

    More on TOPAZ-1

    Canadian Cancer Society: Gallbladder Cancer Statistics

    Canadian Cancer Society: Bile Duct Cancer Statistics

    Zeynep is a Scientific Communication Specialist with the Princess Margaret Cancer Foundation. Formerly, she conducted research in various cancer labs, focusing on areas in immunotherapy, molecular biology and genetics, with research experience in ovarian cancer, breast cancer, osteosarcoma and stem cells. She is a strong supporter of science communication and making research accessible to everyone. She has been a RIOT team member for over 8 years.


    Leave a Reply

    Fill in your details below or click an icon to log in:

    WordPress.com Logo

    You are commenting using your WordPress.com account. Log Out /  Change )

    Twitter picture

    You are commenting using your Twitter account. Log Out /  Change )

    Facebook photo

    You are commenting using your Facebook account. Log Out /  Change )

    Connecting to %s