The Cholangiocarcinoma Foundation – Your Donations at Work

A press release is to follow however; I couldn’t wait to share some of the news with you:

2012 Cholangiocarcinoma Foundation Grants and Project Funding

Grant $40,000 – UCSF Hepatobiliary Tissue Bank

Advancing Translational Science in Cancers of the Biliary Tract through Biorepository of Human Tumor and Blood Specimens
Supports: the UCSF Hepatobiliary Tissue Bank (CC#124512)
Medical Team: Drs. Alan Venook (Medical Oncology), Katie Kelley (Medical Oncology), Robert Kerlan (Interventional Radiology), and Linda Ferrell (Pathology) at UCSF

The overall goal of the HBTB is to advance our understanding of this rare and under-studied tumor type by developing a longitudinal biorepository of human tumor and blood specimens linked to clinical, pathologic, and demographic data from which current and future researchers, both within and outside of UCSF, can obtain high quality biospecimens and data. Specimens banked under this hepatobiliary tissue bank will be made available to UCSF and non-UCSF investigators in the future to perform laboratory studies including analyses of proteins, genetic mutations, gene expression, epigenetic features, or the growth of normal and malignant cells. This unique resource is expected to enable future biomarker discovery and validation studies (including paired metastatic and primary tumors when available), linked with clinical and pathologic data including survival.

An immediate goal of the HBTB is to collect high quality frozen cholangiocarcinoma specimens along with paired normal tissue (blood or normal liver) to support the opening of a cholangiocarcinoma cohort within the National Cancer Institute’s The Cancer Genome Atlas (TCGA). A long-term goal is to partner with researchers from other institutions by sharing biospecimens and data for high priority collaborative research efforts which are critical to advancing the field in this rare tumor type. To these ends, the HBTB infrastructure and informed consent process have been designed to allow for future sharing of specimens across institutions as well as collection of data in a centralized database.

Real-time collection and freezing of biliary tract tumors in the operating room, specimen processing, and banking of fresh frozen tissue and blood specimens for approximately 20 patients with biliary tract cancers undergoing a therapeutic procedure at UCSF in 2013

An adequate amount (at least 100 mg tumor tissue) of these banked specimens will be held in reserve and allocated preferentially to The Cancer Genome Atlas (TCGA) upon opening a cholangiocarcinoma cohort in the future

Specimen allocation will also be prioritized to collaborative projects across institutions, based upon our belief that the sharing of specimens and data will achieve the highest quality science in this rare tumor type

The development of informatics infrastructure development to link HBTB Tissue Core Database with the web-based OnCore Clinical Trials Database

Grant $44,202 – Hepatobiliary Neoplasia Registry and Biorepository
International Hepatobiliary Neoplasia Registry and Biorepository

Supports: Mayo Clinic, Rochester, MN
Medical Team: Dr. Lewis R. Roberts, MB ChB, PhD

The overall goal is to support the collection of clinical information and samples of blood and tissue from patients with hepatobiliary neoplasia in an IRB approved International Hepatobiliary Neoplasia Registry and Biorepository. Patients will complete a detailed scannable risk factor, family history and clinical history questionnaire and provide blood samples for processing into serum, plasma and DNA. If patients also have surgery or in some cases, biopsies, tissue specimens will be collected from tumor and adjacent benign/normal tissue. Tissue specimens not needed for clinical diagnostic purposes are quick frozen in liquid nitrogen, usually within 30 to 40 minutes after acquisition. Samples from the repository will be used for basic and translational studies encompassing the spectrum from research into basic pathogenetic mechanisms of hepatobiliary carcinogenesis, early detection and diagnosis of hepatobiliary cancers, prognostic prediction, and prediction of treatment outcome.

Research Plan: The collected samples will be used for three main types of studies:

1. DNA samples from patients with cholangiocarcinoma will be used for a genome-wide association study to determine the genetic variants that confer risk for cholangiocarcinoma.

2. Serum samples from patients with cholangiocarcinoma will be used to validate new biomarkers for early detection and diagnosis of cholangiocarcinoma.

3. Tissue samples obtained at surgical resection will be implanted into immunodeficient mice to create patient derived xenografts and will also be snap frozen in liquid nitrogen for future comprehensive genome-wide molecular analyses such as is performed by the National Cancer Institutes Cancer Genome Atlas Project (TCGA).

Grant $40,000 – Cell Lines and Novel Antibodies
Establish new cholangiocarcinoma cell lines from cholagniocarcinomas surgically removed from patients and evaluate novel antibodies to treat cholangiocarcinoma.

Supports: Massachusetts General Hospital
Medical Team: Dr. Cristina Ferrone, M.D. , PI.; Matteo Ligorio, M.D. Postdoctoral Fellow; Dr. Nabell El-Bardeesey

The support will test a novel immunotherapeutic strategy which targets not only differentiated cholangiocarcinoma cells, but also cholangiocarcinoma stem cells (CSCs). Our research group has been able to establish two novel cell lines from a primary cholangiocarcinoma and a cholangiocarcinoma metastasis.

Aim 1
To develop novel cholangiocarcinoma cell lines, which we will test with a panel of tumor antigen specific monoclonal antibodies.

Cell Line development with Dr Nabeel El-Bardeesey
To address the paucity available cholangiocarcinoma cell lines, we have developed optimized conditions for the establishment of new lines from surgical specimens and biopsies.

Specific Aim 1: To develop novel cholangiocarcinoma cell lines
We have optimized the conditions and have been able to establish a cell line from an intrahepatic cholangiocarcinoma and from a cholangiocarcinoma metastasis to the bone. We plan to develop an additional 10 novel cell lines from surgically resected cholangiocarcinomas.

Aim 2
To determine if cholangiocarcinoma cell lines express clinically relevant tumor antigens identified by our panel of monoclonal antibodies.

Specific Aim 2: To test cholangiocarcinoma cell lines with a panel of tumor antigen specific monoclonal antibodies to determine if and which tumor antigens are expressed by cholangiocarcinoma cell lines.

Aim 3
To determine if cancer stem cells are present in cholangiocarcinoma cell lines and to test whether cancer stem cells can be eliminated by specific monoclonal antibodies.

Future directions.
Additional experiments, not part of this application, will test whether the strategy found to be effective in eliminating CICs in vitro is also effective in eliminating CICs when cholangiocarcinoma cell lines are grafted in immunodefficient mice. To prove the clinical relevance of the results obtained with the cell lines experiments will be repeated utilizing cholangiocarcinoma tumors removed from patients.

Grant $60,000 – ASCO YIA
Young Investigator Award
Supports: American Society of Clinical Oncology
Medical Team: TBD

The one-year $60,000 grant is intended to raise awareness and trigger progress against this cholangiocarcinoma, while providing critical early funding for physician-scientists at the beginning of their careers. Many successful programs have funded researchers early in their investigative careers. Providing early career grants help encourage investigators to focus their careers on bile duct cancer. The Conquer Cancer Foundation of the American Society of Clinical Oncology Grants Selection Committee will determine the recipient by evaluating the scientific merit of the Young Investigator Award applications using a two-part peer-review process. Recipients of the Young Investigator Award will be announced in April 2013.

Hugs,
Marion