Novel synergistic combination therapy in fibrolamellar carcinoma

Timeframe: 2022 – 2023 Goal: Knock-out gene targets in a mouse model of FLC to identify potentially effective drug combinations for patients with advanced FLC Principal Investigator: Sean Ronnekleiv-Kelly, MD Study overview: This study will apply an innovative gene-editing based technology (genome-wide CRISPR knockout screen) on a mouse cellular model to screen all possible cancer …

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Identifying therapeutic vulnerabilities in fibrolamellar carcinoma

Timeframe: 2020 – 2024 Goal: Investigate the impact on FLC growth and survival of inhibiting two specific oncogenes identified in previous works Principal Investigator: Praveen Sethupathy, PhD Study overview: Based on previous epigenomic, metabolomic, and microRNA profiling, as well as initial drug studies, the study team has developed two new exciting hypotheses about therapeutic vulnerabilities …

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Molecular therapies for fibrolamellar carcinoma (FLC) – continuation

Timeframe: 2023 – 2025 Goal: Investigate alternate means of therapeutically targeting DNAJ-PKAc Principal Investigator: John Scott, PhD Study overview: Previous work has established that the fusion protein interacts with large number of binding partners as compared to the native protein by increased association with the AKAP proteins (the latter acts as a scaffold). One of …

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Molecular therapies for fibrolamellar carcinoma (FLC) – extension

Timeframe: 2021 – 2023 Goal: Investigate the potential of heat shock protein 70 (Hsp70) and kinase inhibitors as potential therapeutic options in pre-clinical models Principal Investigator: John Scott, PhD Study overview: In the previously funded work, the investigators discovered that DNAJ-PKAc forms a complex with heat shock protein 70 (Hsp70) and mitogenic kinases (kinase enzymes …

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Molecular therapies for fibrolamellar carcinoma (FLC)

Timeframe: 2019 – 2021 Goal: Investigate the potential of heat shock protein 70 (Hsp70) and mitogen-activated protein kinases (MAPKs) as therapeutic options for FLC Principal Investigator: John Scott, PhD Study overview: A main goal of this project was to determine how the abnormal form of protein kinase A (PKA) present in fibrolamellar carcinoma (FLC) cells …

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Expansion conditions for fibrolamellar carcinoma (FLC) organoids

Timeframe: 2019 – 2020 Goal: Identify optimal culture conditions for FLC organoidsPrincipal Investigator: Jian Liu, PhD Study overview: Scientific investigators often use cultures, dishes containing tumor cells, to test candidate treatments for a disease. The type of cultures that most accurately reflect the properties of cells as if they were inside the body are “organoids”, …

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Validating the RNA signature of fibrolamellar hepatocellular carcinoma

Timeframe: 2015 – 2017 Goal: Validating the RNA signature, expression and function in FLCPrincipal Investigator: Praveen Sethupathy, PhD Study overview: In past work at UNC, a survey of numerous drugs under consideration for FLC use proved non-effective or minimally effective in limiting the growth of the first FLC tumor model. This indicated that completely new …

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Bioinformatic and molecular analysis of FLC

Timeframe: 2010 – 2011 Goals: Research coordination and molecular analysis for FLC Principal Investigators: W. David Hankins, MD 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 …

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International Cancer Alliance for Research and Education (ICARE) research effort coordination

Timeframe: 2010 – 2011 Goals: Identify and launch initial fibrolamellar carcinoma research efforts Principal Investigators: W. David Hankins, MD 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 …

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