A founding goal of TCF is realized as researchers identify potential drug targets and uncover novel disease subtypes through in-depth genetic and cellular analysis of a large collection of biliary tract cancer cell lines, paving the way for more personalized treatments.
“Generation of a Biliary Tract Cancer Cell Line Atlas Identifies Molecular Subtypes and Therapeutic Targets“, published in Cancer Discovery, a journal of the American Association for Cancer Research, announces the global release of the Cholangiocarcinoma Cell Line Atlas. The article identifies two new subtypes of this rare cancer and defines a series of potential drug targets that will inform new treatment options.
“In the final months of his life, our founder, Paul Poth set out to speed research and innovation for people facing rare cancers like his by creating TargetCancer Foundation. Our very first grant was given by Paul in 2009 to the Center for Molecular Therapeutics (CMT) at Massachusetts General Hospital (MGH). The CMT was testing existing cancer therapies against various cancer cell lines in search of therapeutic “hits.” And Paul was determined to get cell lines from his rare cancer, cholangiocarcinoma (a subtype of biliary tract cancer), added to the CMT screen to help scientists find treatments.
After Paul’s death, his wife, Kristen, and brother-in-law, Jim, stayed focused on his vision, seeking new scientific partners to increase the availability of cell lines. That was how they met Nabeel Bardeesy, PhD of Massachusetts General Hospital Cancer Center in 2010. Then an early career scientist, Dr. Bardeesy was willing to take a chance on a little-known cancer and dedicate his lab to studying it. TCF enthusiastically began funding his emerging work.
What is a cell line?
Cell lines are essential tools in cancer research. They are groups of cells taken from human tumors and grown in labs. They help scientists understand how cancers behave, and more importantly, how they can be treated. Though cell lines for common cancers are easy to find, for rare cancers like cholangiocarcinoma, there are often only a few available and are insufficient to represent the diversity of the disease.
Thanks to Paul’s vision and The Bardeesy Lab’s partnership, we have made great strides against cholangiocarcinoma. Years of research funding totaling over $1.1 million from TCF, and discoveries from Dr. Bardeesy and his team have helped TCF and the Bardeesy Lab grow together. This funding contributed to the development of a robust set of research tools and data for cholangiocarcinoma. Under Dr. Bardeesy’s leadership, a multidisciplinary group of experts has come together to work on this effort. Collaborators include prominent figures like Gad Getz, PhD and Francisca Vazquez from the Broad Institute of MIT and Harvard, Wilhelm Haas from MGH, and young scientists in their teams, Vindhya Vijay and Negin Karisani.
With funding from TCF, The Bardeesy Lab, Cristina Ferrone, a cancer surgeon at MGH, and other colleagues created the first Cholangiocarcinoma Cell Line Bank in 2012. New animal models—genetically engineered mouse models and xenografts—followed. These research tools have been transformative for patients. They not only sparked discoveries in the lab but also helped guide the development of clinical trials which have enabled two new cholangiocarcinoma treatments to be approved by the U.S. Food and Drug Administration for mutations identified through Dr. Bardeesy’s work.
This month, the Bardeesy Lab and TCF achieved another major milestone. After nearly 15 years of collaboration, we are proud to share the global launch of the Cholangiocarcinoma Cell Line Atlas.
The cell line collection, comprising new models developed by Dr. Bardeesy’s team as well as those obtained from international sources, underwent a series of genetic tests and functional screens that classified the cell lines and identified the critical genes each one depends on for survival. This work was conducted through the Broad Institute’s Cancer Dependency Map (DepMap) program, and analyzed by Dr. Getz’s team.
Researchers from around the world can now access the results of these detailed analyses and the associated data from more than 60 biliary tract cancer cell lines – including primarily cholangiocarcinomas- through the open-access DepMap portal. DepMap also enables researchers to explore and compare data from more than 1000 additional cell lines from other cancers, offering datasets and tools for analysis and visualization. DepMap uses a wide range of cancer models that reflect the diversity of human cancers. Additionally, the new biliary tract cell lines are being made available to researchers worldwide through a publicly accessible cell line bank, DSMZ.
Making the Cholangiocarcinoma Cell Line Atlas and cell line collection available through these mechanisms will enable deeper exploration of cholangiocarcinoma biology compared to other cancers. And it will speed the creation of more effective treatments, each tailored to specific patients.
This month, in a landmark paper published in Cancer Discovery, a journal of the American Association for Cancer Research, Bardeesy and his team revealed that, thanks to the Atlas, they discovered two distinct subtypes of cholangiocarcinoma—Bi-lineage and Ductal. Each subtype behaves differently and has its own clinical traits, providing vital information that can help improve and personalize treatment for this complex cancer.
“This project would not have been possible without the support of TargetCancer Foundation. We shared a common vision for advancing the field, and it was an honor to collaborate toward this important goal.”
Nabeel Bardeesy, Ph.D.
Gallagher Endowed Chair in Gastrointestinal Cancer Research
Massachusetts General Hospital Cancer Center;
Associate Professor, Harvard Medical School
This achievement is a testament to the power of scientific collaboration and investment. Rare cancers are often overlooked and under-resourced, and discovery takes time. But good science builds on itself. With dedication and collaboration, even modest, sustained funding can yield deeply meaningful breakthroughs. We are so proud to have played a part in this milestone accomplishment.
“From the moment we met Dr. Bardeesy in 2010, there was a feeling of trust and possibility. Everything we experienced when Paul was diagnosed was negative. No cholangiocarcinoma treatment protocol. No research. No options. Meeting Nabeel felt like taking some control back from an impossible situation. He had a very clear sense of what was needed to make an impact on this rare cancer, and we were proud to invest in his work and vision. I am so incredibly grateful that after 15 years of partnership, funding, and friendship, the global research community has access to the Cell Line Atlas. Paul knew these cell lines were essential for understanding his disease and finding life-saving treatments for patients. The discoveries they enable are a truly meaningful part of his legacy that will continue to live on through the work yet to come.”
Kristen Palma
President, TargetCancer Foundation
The acknowledgment displayed below is featured in the “Generation of a biliary tract cancer cell line atlas identifies molecular subtypes and therapeutic targets” article published in Cancer Discovery, a journal of the American Association for Cancer Research.
