Pediatric Surgical Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Stem Cell Reports. 2022 Aug 9;17(8):1874-1888. doi: 10.1016/j.stemcr.2022.06.003. Epub 2022 Jul 7.
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.
纤维板层肝细胞癌（FLC）是一种罕见的、常致命的肝癌，主要影响青少年和年轻人，目前尚无批准的治疗方法。由于缺乏体外模型，治疗方法的开发受到阻碍。类器官已被证明可作为研究许多疾病的模型系统。在这项研究中，在手术时获得肿瘤组织和相邻的非肿瘤肝脏。组织被分离并作为类器官生长。我们开发了 21 条患者来源的类器官系：12 条来自转移灶，3 条来自肝肿瘤，6 条来自相邻的非肿瘤肝脏。这些患者来源的 FLC 类器官重现了患者肿瘤的组织形态、免疫组织化学和转录组。患者来源的 FLC 类器官被用于初步的高通量药物筛选，以证明识别治疗方法的概念验证。这个模型系统有可能提高我们对这种罕见癌症的认识，并为药物测试和开发带来重大前景。
