Disease mechanism and target research Archives - Page 3 of 5

Therapeutic Action of Tumor-Specific Amplitude Modulated Radio Frequency Electromagnetic Fields in Fibrolamellar Carcinoma

Goal: Investigate the applicability of using an FDA-approved device to treat fibrolamellar patients Principal Investigator: Hugo Jimenez, PhD Grant length: One year, plus extension Study overview: In this study, Dr. Jimenez and his team will conduct initial feasibility testing with a device that delivers low energy amplitude modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF …

Retinoic acid-induced loss of DNAJB1-PRKACA fusion protein expression

Goal: Investigate the potential of retinoic acid therapy Principal Investigators: Andrew Yen, PhD and Praveen Sethupathy, PhD Grant length: One year 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 …

Characterization of mitochondria alterations and their functional consequences in fibrolamellar carcinoma (FLC) and FLC-like BAP1 hepatocellular carcinoma

Goal: Identify functional role of mitochondrial alterations in FLC and FLC-Like BAP1 HCC Principal Investigator: Jessica Zucman-Rossi, MD, PhD Grant length: One year 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 …

Development and Characterization of Patient-derived Models of Fibrolamellar Carcinoma

Goal: Evaluate selective inhibitors of polo-like kinase 1 (PLK1) for effectiveness in human models of FLC Principal Investigator: Taran Gujral, PhD Grant length: Two years 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 …

Disruption of PKA RIα phase separation by the oncogenic fusion protein in FLC

Goal: Determine the molecular mechanisms of FLC and identify new pharmacological agents that could lead to effective therapeutics Principal Investigator: Jin Zhang, PhD Grant length: Two years 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 …

Selective translational inhibition as a treatment strategy for fibrolamellar liver cancer

Goal: Testing the drug zotatifin (eFT226) against human FLC tumors grown in mice Principal Investigator: John Gordan, MD, PhD Grant length: One year 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 …

Elucidation of nuclear-mitochondrial signaling by DNAJ-PKAc to define targeted vulnerabilities in FLC

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 Grant length: Two years Study overview: Signals that control the growth and metabolism of cells often are relayed through a series of reactions in which proteins are sequentially …

Molecular therapies for fibrolamellar carcinoma (FLC) – extension

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 Grant length: Two years 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 …

Molecular therapies for fibrolamellar carcinoma (FLC)

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 Grant length: Two years 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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