Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient Derived Xenografts and Direct from Patient Screening

This recent publication describes six new PDX lines derived by direct implantation of tumor specimens, both from the liver (one primary and one recurrent tumor) and metastases. These facilitated the first reported large-scale screening of compounds for the ability to kill dissociated FLC tumor cells in short-term culture (72 hours). Active compounds were also assessed …

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A framework for fibrolamellar carcinoma research and clinical trials

This article, published in Nature Reviews Gastroenterology & Hepatology, summarizes the key advances made in understanding the disease since the 2014 discovery that nearly all FLC tumors contain the DNAJB1-PRKACA chimeric fusion transcript. The paper outlines the advances made in understanding the molecular pathways driven by the fusion protein and the potential to identify actionable …

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MicroRNA-375 Suppresses the Growth and Invasion of Fibrolamellar Carcinoma

While the significance of the DNAJB1-PRKACA fusion gene in fibrolamellar carcinoma has been established and validated, the role of microRNAs (miRNAs) in FLC remains unclear. MicroRNAs have been implicated as drivers in many diseases including a variety of cancers. This study analyzed small RNA sequencing data to identify dysregulated miRNAs in FLC tumors and identified …

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Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma

This study was the first published research effort that identified the DNAJB1-PRKACA chimeric transcript in fibrolamellar carcinoma tumors. By performing RNA sequencing on tumor and healthy tissue samples, a chimeric transcript was discovered that had not been previously reported in the literature. This fusion transcript arises due to a ~400-kilobase deletion on chromosome 19.  In …

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CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates that the DNAJB1-PRKACA Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

The DNAJB1-PRKACA fusion gene is found in almost all FLC tumors. In order to determine if this gene fusion is a cause of the tumors, these researchers used a CRISPR-Cas9 technique to create a chimeric DNAJB1-PRKACA fusion gene in the livers of otherwise healthy mice. Using the CRISPR-Cas9 system, the researchers created guide RNAs that …

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Predictors of Outcome in Patients With Fibrolamellar Carcinoma: Analysis of the National Cancer Database

This publication retrospectively analyzes the clinicopathological factors and treatments affecting overall survival in FLC. Using the National Cancer Database, it identified 496 patients diagnosed with FLC between 2004 and 2015. Of those patients, resection was performed on 254 (51.2%), liver-directed therapy on 13 (2.6%), and liver transplantation on 15 (3.0%) patients. Median overall survival times …

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