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: 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 …
Timeframe: 2024 – 2026 Goal: Determine if targeting CDK7 could be a useful treatment approach for FLC. Principal Investigator: Sean Ronnekleiv-Kelly, MD Study overview: Unregulated proliferation of cells is a hallmark of cancer. In other words, cancer cells continue to divide and increase in number when normal cells would stop dividing. A family of 20 …
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 …
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 …
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 …
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 …