ICARE

Goals: Perform molecular analysis for FLC

Principal Investigators: W. David Hankins, MD

Grant length: One year

Study overview: In addition to coordinating ICARE’s fibrolamellar exploration efforts (described separately) during FCF’s one-year partnership with ICARE, Dr. Hankins’ lab received a “Freedom of Pursuit” unrestricted grant, intended to fund bioinformatics and molecular (DNA, RNA and Protein) analyses of fibrolamellar tissue. Planned efforts included locating FLC cells within a particular lineage or developmental pathway from liver stem cells (pathways that produce various mature liver cells such as epithelial, stromal, stellate, etc.). The ultimate goal of their effort was to discover new, lineage specific targets which could be exploited to kill or eradicate the fibrolamellar tumors.

Results: Several cellular and molecular mapping strategies were launched, including the analysis of cytokine, growth factor or hormone receptors, and ligands expressed by fibrolamellar. Limited documentation of those results was received. More detailed and useful work on the potential lineage of FLC was completed by the Reid lab at the University of North Carolina.

However, Dr. Hankins identified and evaluated the development of potential new therapeutic options in other labs/institutions that he felt could be useful for doctors treating FLC patients. Those potential approaches included:

• Exploration of 3-Bromopyruvate as a treatment of tumors through exploitation of a common property of cancer cells called the Warburg effect. This therapeutic approach began with the publication by Dr. Young Ko and Peter Pedersen of John Hopkins of promising results in mice in 2004 and subsequent studies in Europe. However the compound has not yet reached clinical trials.
• Exploration of potential applicability to FLC of the invention of nanotechnology particles (by the lab of Dr. Mark Davis of Caltech) that can specifically target and deliver a “killer gene” cancer cells.
• Analysis of the use of an intensive regimen of certain lipids, exercise, and other compounds to bring about the death of cancer cells, which unlike normal cells, are extremely susceptible to the high levels of unsaturated fatty acids generated by this therapy.

Note: This study was one of four “Freedom of Pursuit” research awards to be distributed under the joint FCF/ICARE program active in 2010/2011. The use of those funds was unrestricted. The FCF/ICARE relationship was discontinued in late 2011.

Since the joint FCF/ICARE relationship ended, no FCF grants have been issued which were unrestricted in their use.

Goals: Identify and launch initial fibrolamellar carcinoma research efforts

Principal Investigators: W. David Hankins, MD

Grant length: Two years

Study overview: The International Cancer Alliance for Research and Education (ICARE) focuses its programs on building and funding local and international medical academic research teams (I-TEAMS) that identify, initiate and fund cutting-edge research projects to support decisions of patient/doctor teams. In January, 2010, the Foundation requested that an ICARE Investigative Team (I-Team) be established to conduct “accelerated personalized translational research” on fibrolamellar carcinoma. After numerous discussions, Dr. Hankins of ICARE began to identify, organize, motivate and mobilize leading global scientists and physicians who had the potential to rapidly identify, or create cutting-edge medical solutions that would contribute to fibrolamellar patients’ survival.

Dr. Hankins’ organizational efforts led to a business plan outline that consisted of four “Freedom of Pursuit” research awards to be distributed under Dr. Hankins guidance as unrestricted research support to the laboratories of selected scientists, plus an amount to cover ICARE’s overhead expenses throughout the project. The goal of this unrestricted funding was to allow FCF/ ICARE to successfully recruit world class scientists and have them contribute their expertise and lab work to answer important questions of clinical significance to cancer research and FLC.

Results: Funded investigators who were given “Freedom of Pursuit” grants funded by this FCF/ICARE effort included:

• Lola Reid, PhD (University of North Carolina)
• Michael Torbenson, MD (Johns Hopkins University)
• Yuzhuo Wang, PhD (University of British Columbia)
• W David Hankins, MD (ICARE).

Two of these grantees, Lola Reid and Michael Torbenson, had significant prior expertise in liver cancer and produced output that advanced the scientific understanding of FLC.

Since the conclusion of the joint FCF/ICARE effort in late 2011, no grants issued by FCF have been unrestricted in their use.