Disease mechanism and target research Archives - Page 5 of 5

DNAJB1-PKAc-β-catenin-ALCD-dependent activation of cancer genes plays an essential role in fibrolamellar hepatocellular carcinoma

Goal: Document mechanisms driving FLC and test if treatment with inhibitors of β-catenin may be a potential therapeutic approach for FLC Principal Investigator: Nikolai Timchenko, PhD Grant length: One year Study overview: In the course of studies of pediatric liver cancer, the team at CCHMC has identified chromosomal regions (Aggressive Liver Cancer Domains, ALCDs) in …

Iodine transporter research

Goal: Investigate the potential of radioactive iodine as a therapeutic in FLC Principle Investigator: Nancy Carrasco, MD (Currently at Vanderbilt University) Grant length: One year Study background: FLC cells express high levels of the iodine transporter NIS, raising the possibility that radioactive iodine may be a potential therapeutic for FLC. Radioactive iodine has a long …

Genomic initiative on Fibrolamellar Hepatocellular Carcinoma

Goal: Identify genetic mutations in FLC Principal Investigator: Sandy Simon, PhD Grant length: One year Study background: The goal of this project was to identify genetic mutations present in FLC. Identification of mutations common in FLC tumors is critical to enhancing the understanding of the underlying biology of this tumor and allow for development of …

Developing therapeutics for fibrolamellar hepatocellular carcinoma

Goal: Develop new therapeutics for FLC Principal Investigator: Sandy Simon, PhD Investigator Collaboration: Barbara Lyons, PhD (New Mexico State University) Grant length: Two years Study overview: The goal of this work was to identify potential therapeutic strategies to target FLC. The team identified three independent approaches to analyze based on their laboratory’s work showing that …

Flipping the switch on PKA: synthetic lethal approaches to block PKA-driven tumor growth in fibrolamellar liver cancer

Goal: Understand growth mechanisms and identify potential therapeutic targets Principal Investigators: John Gordan, MD, PhD (UCSF) and Nabeel Bardeesy, PhD (Mass General Hospital) Grant length: Two years Study overview: The discovery of a genetic change in the protein kinase A (PKA) gene in nearly all cases of fibrolamellar liver cancer (FLC) creates hope that targeted …

Characterizing enzyme inhibition of the DnaJPKAc chimeric protein derived from fibrolamellar hepatocellular carcinomas

Goal: Characterize inhibition of the DnaJ-PKAc chimeric protein in fibrolamellar carcinoma Principal Investigator: Hibba tul Rehman, MD Grant length: One year Study overview: The DNAJB1-PRKACA fusion gene produces the DNAJ-PKAc fusion kinase protein, which is present in nearly all FLC tumors and promotes liver tumor formation in mice. Kinases, including fusion kinases, have been successful …

Kinase fusion function investigation

Goal: Investigate DNAJB1-PRKACA fusion kinase function in new fibrolamellar carcinoma models Principal Investigator: Yi Guo, PhD Grant length: One year Study overview: The DNAJB1-PRKACA fusion kinase is found in nearly 100% of FLC cases. While this novel fusion had previously been shown to promote tumors in mice, defining the mechanistic function of DNAJB1-PRKACA and the …

Hedgehog and YAP signaling in fibrolamellar carcinoma: tumor-stroma crosstalk and the cancer stem cell niche

Goal: Evaluate the role of Hedgehog and YAP signaling in fibrolamellar carcinoma Principal Investigators: Cynthia Guy, MD and Anna Mae Diehl, MD Grant length: Two years Fibrolamellar carcinoma has a unique histological appearance consisting of large tumor cells surrounded by thick fibrous bands, the stroma. Molecular crosstalk between tumor and stroma is important in tumor …

Micro RNAs and long non-coding RNAs role in fibrolamellar and evaluation of RNA-based therapeutics

Goal: Investigate the role of microRNAs and long non-coding RNAs in fibrolamellar carcinoma and evaluate RNA-based therapeutics Principal Investigator: Praveen Sethupathy, PhD Grant length: Two years Study overview: This study aimed to leverage genome-scale approaches to discover the molecular factors most critical to FLC tumor formation, metastasis, and drug resistance. MicroRNAs and long non-coding RNAs are …

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