Timeframe: 2019 – 2023 Goal: Investigate the potential of retinoic acid therapy Principal Investigators: Andrew Yen, PhD and Praveen Sethupathy, PhD Study overview: FLC is driven by the DNAJ-PKAc fusion protein. A potential therapeutic strategy would be to induce loss of this key driver protein. One approach to substantially alter gene expression in cancer cells …
Timeframe: 2022 – 2024 Goal: Identify functional role of mitochondrial alterations in FLC and FLC-Like BAP1 HCC Principal Investigator: Jessica Zucman-Rossi, MD, PhD Study overview: Recently, important research studies have reported specific genomic abnormalities of tumor subtypes. One of these, representing the fusion between DNAJB1 and PRKACA genes, has been described to be typical of …
Timeframe: 2021 – 2024 Goals: Determine the molecular mechanisms of FLC and identify new pharmacological agents that could lead to effective therapeutics Principal Investigator: Jin Zhang, PhD Study overview: In recent studies, the investigation team discovered that the presence of the FLC oncogenic fusion protein disrupts a membraneless organelle. They showed that loss of this …
Timeframe: 2023 – 2025 Goal: Evaluate selective inhibitors of polo-like kinase 1 (PLK1) for effectiveness in human models of FLC Principal Investigator: Taran Gujral, PhD Study overview: Abormal cell signaling by the DNAJ-PKAc fusion protein kinase drives the uncontrolled growth of fibrolamellar carcinoma. Thus far, however, drugs that inhibit the fusion kinase also block the …
Timeframe: 2023 – 2024 Goal: Testing the drug zotatifin (eFT226) against human FLC tumors grown in mice Principal Investigator: John Gordan, MD, PhD Study overview: This “proof of concept” study focuses on testing the drug zotatifin (eFT226) for activity against human FLC tumors grown in mice. This drug is being developed by eFFECTOR Therapeutics (Solana …
Timeframe: 2022 – 2025 Goals: Identifying how the DNAJ-PKAc/SIK/p300 program controls mitochondrial function and define how these abnormal mitochondria affect the metabolism of FLC cells Principal Investigator: Nabeel M. Bardeesy, PhD Study overview: Signals that control the growth and metabolism of cells often are relayed through a series of reactions in which proteins are sequentially …
Timeframe: 2024 – 2026 Goals: Streamline the collection, analysis and sharing of FLC data across institutions while supporting the broader goals of open science and collaborative research within the FLC research network Principal Investigators and Partners: FCF; Velsera; Praveen Sethupathy, PhD, Cornell University; Taran Gujral, PhD, Fred Hutchinson Cancer Center Study Overview: This study intends …
Timeframe: 2020 – 2023 Goal: Create a comprehensive list of potential drug targets for FLC Principal Investigator: Jesse Boehm, PhD Study overview: This project is part of the Broad Institute’s Rare Cancer Dependency Map Initiative. The project has three main goals to identify potential FLC therapeutics: If fully successful, this effort will nominate high priority …
Timeframe: 2024 – 2025 Study overview: Since the discovery in 2014 of the fusion gene (DNAJB1-PRKACA) that drives fibrolamellar carcinoma (FLC), a drug that would selectively inhibit or destroy the chimeric protein (DNAJ-PKAc) encoded by that gene has been considered a “holy grail” for FLC therapy. Such a drug must effectively target DNAJ-PKAc, while only …