Fibrolamellar carcinoma (FLC) is a rare, often lethal, liver cancer affecting adolescents and young adults, for which there are no approved therapeutics. The development of therapeutics is hampered by a lack of in vitro models. Organoids have shown utility as a model system for studying many diseases. In this study, tumor tissue and the adjacent non-tumor liver were obtained at the time of surgery. The tissue was dissociated and grown as organoids. We developed 21 patient-derived organoid lines: 12 from metastases, three from the liver tumor and six from adjacent non-tumor liver. These patient-derived FLC organoids recapitulate the histologic morphology, immunohistochemistry, and transcriptome of the patient tumor. Patient-derived FLC organoids were used in a preliminary high-throughput drug screen to show proof of concept for the identification of therapeutics. This model system has the potential to improve our understanding of this rare cancer and holds significant promise for drug testing and development.
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http://dx.doi.org/10.1016/j.stemcr.2022.06.003 | DOI Listing |
Nat Commun
December 2024
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY, USA.
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis.
View Article and Find Full Text PDFFibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC.
View Article and Find Full Text PDFLancet
December 2025
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Cancer and Blood Disorders Center, and Harvard Medical School, Boston, MA, USA.
Cancer Rep (Hoboken)
December 2024
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) clinically occurs in young people aged 20-30 years, who often have a normal liver background. We propose a treatment for such cases in which a combination therapy of atezolizumab and bevacizumab is followed by sandwiching radiation therapy to release tumor antigens and then re-administering the combination therapy of atezolizumab and bevacizumab (ABC conversion therapy).
Case: The patient is a 15-year-old girl.
Front Immunol
November 2024
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Fibrolamellar carcinoma (FLC) is a rare but fatal cancer that occurs primarily in young people. There are currently no known effective treatments, although several promising treatments appear to be in development. Genetic studies have confirmed that almost all FLC tumors have a fusion protein marker (DNAJB1-PRKACA) encoded by a fusion gene (DNAJB1-PRKACA); It is currently accepted as a diagnostic criterion for FLCs.
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