Genomic/Immunological Heterogeneity of Intrahepatic Cholangiocarcinoma: Clinical and Translational Studies by International Cholangiocarcinoma Research Network
Abstract
Scientific objective and rationale for this project: The topic area being addressed in this proposal is the second most common type of primary liver cancer that arises from the bile ducts, known as intrahepatic cholangiocarcinoma. Cholangiocarcinoma is a difficult disease to treat; most patients are diagnosed when the cancer is advanced, and current treatment options with chemotherapy have a limited impact on survival. This cancer occurs more commonly in Asia but is rapidly increasing in numbers in the United States. New therapies and a better understanding of the biology of this cancer are needed. Recently, immunotherapy, which harnesses the body’s own immune system against the cancer cells, has shown impressive survival benefit in several cancers, including lung cancer, melanoma, and the more common type of liver cancer, hepatocellular cancer. There has been limited experience with immunotherapy in cholangiocarcinoma, and responses have been very few and clinical benefit to patients with this cancer has been very limited. This proposal is being initiated on behalf of the International Cholangiocarcinoma Research Network (ICRN), a network of over 40 cancer centers worldwide that was created to improve patient survival from this cancer through innovative research. In this application, we are investigating the role of immunotherapy to get a better understanding of the biology of this cancer. Currently there is a paucity of information regarding the type of immune cells known as T cells, which are seen in this cancer, or how these immune cells are related to the tumor genes. A critical understanding is needed to further this research. In this proposal, we are undertaking a large international effort to test tissue samples using methods described by the investigators for the evaluation of immune cells and genetics. This proposal is very translational, as our team will directly work with patients enrolled in three international clinical trials of immunotherapy for cholangiocarcinoma, and the funds from the U.S. Department of Defense will allow us to conduct laboratory tests on their samples to determine which patients will respond, which patients will not, and how we can use such information to ensure optimal patient selection in future immunotherapy trials. We will also conduct additional tests in laboratory animals to determine what other novel immunotherapy combinations can be used in the clinic for cholangiocarcinoma patients. The ultimate applicability of this research, risks, projected time, and contribution to topic areas: Currently, 80% of intrahepatic cholangiocarcinoma patients present with advanced disease that is inoperable by surgery. The average survival of these patients with chemotherapy alone is less than a year. Therefore, there is a critical need to develop new therapies and an urgent need to develop new therapies for this lethal disease. The risks for patients to participate in this research are limited. Any clinical trial or biopsy procedure carries risks. However, these risks are largely mitigated by the fact that the trials included are already ongoing or based on prior experience with the study drugs, which we regard as safe. We have already initiated the laboratory work, clinical trials are ongoing, and we expect this proposal to be completed well within its described timelines. Intrahepatic cholangiocarcinoma is a Peer Reviewed Cancer Research Program topic that falls within the definition of primary liver cancer. This is an “orphan” tumor and an area of great unmet need. We believe that the three clinical trials that are being conducted in this application will greatly enhance our understanding of this cancer, and if our planned experiments are successful, this proposal could change the treatment algorithm for this cancer within the next 5 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910492
Entities
People
- Nilofer Azad
Organizations
- Johns Hopkins University
- United States Army