Cholangiocarcinoma Research

Cholangiocarcinoma is a prime example of what makes a rare cancer so challenging: an absence of basic research tools, published information, and funding that results in a lack of treatment options. Since 2011, TargetCancer Foundation has addressed these challenges by investing over $1.1 million in cholangiocarcinoma research.

Nabeel Bardeesy, PhD
, Gallagher Endowed Chair in Gastrointestinal Cancer Research, Massachusetts General Hospital Cancer Center;
 Associate Professor, Harvard Medical School

A founding goal of TargetCancer Foundation was to change the research landscape for this disease through a long-term commitment to the Bardeesy Lab at the Massachusetts General Hospital Cancer Center. Through strategic seed funding to Dr. Nabeel Bardeesy’s lab, research has progressed faster than ever expected by focusing on key research elements necessary to build a comprehensive research program:

Cell lines and patient-derived xenografts. The TargetCancer Foundation Cholangiocarcinoma Cell Line Bank was established in 2012 in response to the need for a collection of well-characterized cholangiocarcinoma cell lines and associated xenografts. In 2019, the development of this comprehensive collection was completed, and work to move the collection fully into the public domain was initiated.

Understanding driver mutations. Among other studies, TargetCancer Foundation has supported research into the functions of the IDH1 and 2 genes, which are mutated in about 30% of intrahepatic cholangiocarcinoma cases. The Bardeesy lab published a groundbreaking paper in Nature (July 2014) on the effects of mutant IDH1/2 in causing cholangiocarcinoma. This research informs the design and interpretation of clinical trials using mutant IDH inhibiting drugs, and holds great promise for future therapies.

As published in Nature in July 2014.

Funding has also been extended to also support research into the role of FGFR2 gene alteration, which appears in about 10% of intrahepatic cholangiocarcinoma cases and has emerged as a significant therapeutic target.

Community building. No single lab can take on the tremendous task of studying a rare cancer. Through programs like the TargetCancer Foundation Think Tank on Cholangiocarcinoma, we have helped build a collaborative community of researchers across disease areas. In addition, TargetCancer Foundation has funded cholangiocarcinoma research outside of the Bardeesy Lab in an effort to foster a greater research community.

Animal models. With our help, the Bardeesy Lab has successfully engineered a series of mouse models representing several different genetic mutations, allowing for a deeper study of the events driving the development of cholangiocarcinoma in humans.

These areas of focus have led to tremendous progress in a relatively short time, and the impact for patients is real. The first clinical trial informed by TargetCancer Foundation-funded research opened in 2014, and several subsequent trials have followed, offering patients new opportunities for more effective treatments. The potential for the Bardeesy Lab to continue driving research forward remains strong, as does TargetCancer Foundation’s support for these initiatives.