横纹肝细胞癌（FLHCC）是一种罕见的肿瘤，发生在无慢性肝病的年轻患者中。高达80-100％的患者出现复发病情，需要进行额外的手术或全身性治疗。目前缺乏全身性治疗选项和临床前治疗研究。我们以前报道了患者源异种移植（PDX）的建立，以进行临床前研究。在本研究中，我们建立了FLHCC PDX模型，并利用这些模型来定义肿瘤特征和评估全身性治疗药物的疗效。 我们从两名患者的FLHCC切除术中获得原发肿瘤和淋巴结转移肿瘤组织。筛选肿瘤溶解物的蛋白质上调情况，并从淋巴结转移和原发肿瘤组织中建立了细胞系。对细胞系进行替西罗莫斯、吉西他滨/奥沙利铂和FOLFIRINOX治疗后，评估其存活能力。从淋巴结转移组织成功建立了两个PDX模型。对于体内实验，用药后的带瘤小鼠进行替西罗莫斯、FOLFIRINOX和吉西他滨/奥沙利铂治疗。 从淋巴结转移FLHCC成功建立了PDX模型，该模型与原始肿瘤表现非常相似。与原发肿瘤相比，淋巴结转移组织中观察到了mTOR的上调。来自淋巴结转移组织的细胞系对替西罗莫斯表现出显著敏感性。对PDX模型的体内实验显示，替西罗莫斯单药治疗对肿瘤有显著响应且毒性较小。 在本研究中，我们展示了建立与FLHCC非常相似的PDX模型的可行性。与原发组织相比，淋巴结转移组织中观察到了mTOR的上调。替西罗莫斯治疗的mTOR抑制剂疗效提示mTOR通路的上调可能是淋巴结转移病灶生长的重要机制，并具有治疗的潜在靶点。 版权所有 © 2023年，国际抗癌研究学会（George J. Delinasios博士），保留所有权利。

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare tumor presenting in younger patients without chronic liver disease. Up to 80-100% develop recurrent disease, necessitating additional surgery or systemic treatment. Systemic options and pre-clinical treatment studies are lacking. We previously described patient-derived xenograft (PDX) development, allowing for pre-clinical studies. Herein, we develop FLHCC PDX models and utilize these to define tumor characteristics and determine the efficacy of systemic agents.Primary and lymph node metastatic tumor tissues were obtained at the time of FLHCC resection in two patients. Tumor lysates were screened for protein upregulation. Cell lines were generated from metastatic and primary tumor tissue. The viability of the cell lines was assessed after treatment with temsirolimus, gemcitabine/oxaliplatin, and FOLFIRINOX. Two PDX models were developed from metastatic tissue. For in vivo studies, tumor-bearing mice were treated with temsirolimus, FOLFIRINOX, and Gemcitabine/oxaliplatin.PDX models were successfully generated from metastatic FLHCC, which closely recapitulated the original tumor. Upregulation of mTOR was seen in metastatic tissue compared to primary tumors. Cell lines from metastatic tissue demonstrated significant sensitivity to temsirolimus. In vivo testing of PDX models demonstrated a significant response to single-agent temsirolimus with minimal toxicity.Herein, we demonstrate the feasibility of developing PDX models that closely recapitulate FLHCC. Upregulation of mTOR was seen in metastatic tissue compared to primary tissue. The efficacy of mTOR inhibition with temsirolimus treatment suggests that the upregulation of the mTOR pathway may be a significant mechanism for growth in metastatic lesions and a potential target for therapeutics.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.