Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
Cancer Discov. 2019 Jul;9(7):852-871. doi: 10.1158/2159-8290.CD-18-1522. Epub 2019 May 3.
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 . 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. drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice...
先前的研究已经描述了肿瘤类器官可以捕获明确的人类癌类型的多样性。在这里，我们描述了长期培养人类黏膜类器官的条件。使用该方案，建立了一组 31 个人类头颈部鳞状细胞癌（HNSCC）衍生的类器官系。该面板重现了先前描述的 HNSCC 的遗传和分子特征。类器官在异种移植后保留其致瘤潜能。我们观察到对包括顺铂、卡铂、西妥昔单抗和放射治疗在内的一组药物的反应存在差异。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。这些观察结果可能激发对 HNSCC 管理的个性化方法，并扩大 HNSCC 药物的范围。意义：这项工作描述了源自 HNSCC 和相应正常上皮的类器官的培养。这些肿瘤类器官在遗传、组织学和功能上重现了疾病。对肿瘤类器官的药物筛选揭示了对目前用于治疗 HNSCC 的治疗方法以及尚未（尚未）用于临床实践的治疗方法的反应。
