Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oral Oncol. 2018 Dec;87:49-57. doi: 10.1016/j.oraloncology.2018.10.018. Epub 2018 Oct 23.
Currently there are no standard biomarkers of head and neck squamous cell carcinoma (HNSCC) response to therapy. This is, due to a lack of adequate predictive tumor models. To this end, we established cancer organoid lines from individual patient's tumors, and characterized their growth characteristics and response to different drug treatments with the objective of using these models for prediction of treatment response.
Forty-three patients' samples were processed to establish organoids. To analyze the character of these organoids, immunohistochemistry, Western blotting, drug sensitivity assays, clonogenic survival assays, and animal experiments were performed. The HPV status and TP53 mutational status were also confirmed in these lines.
HNSCC organoids were successfully established with success rate of 30.2%. Corresponding two-dimensional cell lines were established from HNSCC organoids at higher success rate (53.8%). These organoids showed similar histological features and stem cell, epithelial and mesenchymal marker expression to the original tumors, thus recapitulating many of the characteristics of the original tumor cells. The cisplatin and docetaxel IC50 were determined for HNSCC organoids and the corresponding 2D cell lines using drug sensitivity and clonogenic survival assays. Responses to drug treatment in vivo were found to be similar to the IC calculated from organoids by drug sensitivity assays in vitro.
We established novel in vitro HNSCC cancer organoid lines retaining many properties of the original tumors from they were derived. These organoids can predict in vivo drug sensitivity and may represent useful tools to develop precision treatments for HNSCC.
目前尚无对头颈部鳞状细胞癌 (HNSCC) 对治疗反应的标准生物标志物。这是由于缺乏足够的预测性肿瘤模型。为此，我们从个体患者的肿瘤中建立了癌症类器官系，并对其生长特征和对不同药物治疗的反应进行了特征描述，目的是使用这些模型来预测治疗反应。
对 43 名患者的样本进行处理以建立类器官。为了分析这些类器官的特征，进行了免疫组织化学、Western blot、药物敏感性测定、克隆形成存活测定和动物实验。还确认了这些系中的 HPV 状态和 TP53 突变状态。
HNSCC 类器官的成功率为 30.2%。成功率更高的二维细胞系是从 HNSCC 类器官中建立的（53.8%）。这些类器官表现出与原始肿瘤相似的组织学特征和干细胞、上皮和间充质标志物表达，从而再现了许多原始肿瘤细胞的特征。通过药物敏感性和克隆形成存活测定，确定了 HNSCC 类器官和相应的 2D 细胞系的顺铂和多西他赛 IC50。体内药物治疗反应与体外药物敏感性测定中从类器官计算出的 IC 相似。
我们建立了新的体外 HNSCC 癌症类器官系，保留了它们源自的原始肿瘤的许多特性。这些类器官可以预测体内药物敏感性，并且可能代表开发 HNSCC 精准治疗的有用工具。
