Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy
Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy
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DOI：
10.1158/2159-8290.cd-18-1522
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发表时间：
2019-07-01
期刊：
影响因子：
28.2
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
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作者：
Driehuis, Else;Kolders, Sigrid;Clevers, Hans
以前的研究已经描述了肿瘤类器官可以捕获定义的人类癌症类型的多样性。在这里，我们描述了人类粘膜类器官长期培养的条件。使用该方案，建立了一组31个头颈部鳞状细胞癌（HNSCC）衍生的类器官系。该图概括了先前描述的HNSCC的遗传和分子特征。类器官在异种移植后保留其致瘤潜力。我们观察了一组药物的差异反应，包括顺铂，卡铂，西妥昔单抗和体外放射治疗。此外，药物筛选揭示了对通常不用于治疗HNSCC患者的靶向药物的选择性敏感性。这些观察结果可能会激发个性化的方法来管理HNSCC和扩大HNSCC drugs.SIGNIFICANCE的剧目：这项工作描述了来自HNSCC和相应的正常上皮细胞的类器官的文化。这些类肿瘤在遗传学、组织学和功能上概括了这种疾病。类肿瘤的体外药物筛选揭示了对目前用于治疗HNSCC的疗法和（尚未）用于临床实践的疗法的反应。
Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs.SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. in vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.