Li Weilin, Nishino Michiya, Reed Eric, Akshinthala Dipikaa, Pasha Hamdan Ahmed, Anderson Erik S, Huang Ling, Hebestreit Hannah, Monti Stefano, Gomez Ernest D, Jalisi Scharukh M, Muthuswamy Senthil K
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Sci Rep. 2025 Jul 7;15(1):24221. doi: 10.1038/s41598-025-88082-5.
Head and neck squamous cell carcinoma (HNSCC) is a prevalent and often fatal malignancy associated with significant treatment-related toxicity. There is an urgent need for a preclinical model to assess therapeutic options and guide clinical decision-making. To define conditions for establishing patient-derived organoid (PDO) models that faithfully recapitulate morphological, histopathological, and genomic characteristics of HNSCC patients and can predict radiation and chemotherapy responses in patients, PDOs were generated from a group of HNSCC patients. The morphological, histological, mutational, and biological characteristics and treatment responses were evaluated. We demonstrate that the PDOs closely resemble resected tumors from which they were derived with respect to histopathology, differentiation state markers, p16 status, and mutation profiling. We observe patient-to-patient variation in cell proliferation rates. Additionally, they exhibit differential responses to radiotherapy and chemotherapy, which were examined using a cell viability assay. This methodology offers potential for drug screening in a pre-clinical context with the potential to mirror clinical outcomes. Our WNT-free growth conditions maintained the differentiation status of PDOs and enabled rapid assessment of drug response and the development of new models to identify new treatment options for head and neck cancer patients.
头颈部鳞状细胞癌（HNSCC）是一种常见且往往致命的恶性肿瘤，与显著的治疗相关毒性有关。迫切需要一种临床前模型来评估治疗方案并指导临床决策。为了确定建立能忠实地概括HNSCC患者的形态、组织病理学和基因组特征并能预测患者放疗和化疗反应的患者来源类器官（PDO）模型的条件，从一组HNSCC患者中生成了PDO。对其形态、组织学、突变和生物学特征以及治疗反应进行了评估。我们证明，PDO在组织病理学、分化状态标志物、p16状态和突变谱方面与它们所源自的切除肿瘤非常相似。我们观察到细胞增殖率存在患者间差异。此外，它们对放疗和化疗表现出不同反应，这通过细胞活力测定进行了检测。这种方法在临床前背景下进行药物筛选具有潜力，有可能反映临床结果。我们的无WNT生长条件维持了PDO的分化状态，并能够快速评估药物反应以及开发新模型以确定头颈部癌症患者的新治疗选择。
