Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses
Abstract 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 establis...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-88082-5 |
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| author | Weilin Li Michiya Nishino Eric Reed Dipikaa Akshinthala Hamdan Ahmed Pasha Erik S. Anderson Ling Huang Hannah Hebestreit Stefano Monti Ernest D. Gomez Scharukh M. Jalisi Senthil K. Muthuswamy |
| author_facet | Weilin Li Michiya Nishino Eric Reed Dipikaa Akshinthala Hamdan Ahmed Pasha Erik S. Anderson Ling Huang Hannah Hebestreit Stefano Monti Ernest D. Gomez Scharukh M. Jalisi Senthil K. Muthuswamy |
| author_sort | Weilin Li |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-21dcfeee4a354d2aa1183ce0d05ee069 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-21dcfeee4a354d2aa1183ce0d05ee0692025-08-20T04:02:56ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-88082-5Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responsesWeilin Li0Michiya Nishino1Eric Reed2Dipikaa Akshinthala3Hamdan Ahmed Pasha4Erik S. Anderson5Ling Huang6Hannah Hebestreit7Stefano Monti8Ernest D. Gomez9Scharukh M. Jalisi10Senthil K. Muthuswamy11Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Medicine, Albert Einstein College of MedicineLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthDepartment of Surgery, Section of Otolaryngology/Head and Neck Surgery, Aga Khan UniversityDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolPancreatic Cancer Center, Henry Ford HealthDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Medicine, Computational Biomedicine Section, Boston University Chobanian and Avedisian School of MedicineDivision of Otolaryngology/Head and Neck Surgery, Beth Israel Deaconess Medical CenterDivision of Otolaryngology/Head and Neck Surgery, Beth Israel Deaconess Medical CenterLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s41598-025-88082-5 |
| spellingShingle | Weilin Li Michiya Nishino Eric Reed Dipikaa Akshinthala Hamdan Ahmed Pasha Erik S. Anderson Ling Huang Hannah Hebestreit Stefano Monti Ernest D. Gomez Scharukh M. Jalisi Senthil K. Muthuswamy Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses Scientific Reports |
| title | Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| title_full | Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| title_fullStr | Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| title_full_unstemmed | Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| title_short | Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| title_sort | head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses |
| url | https://doi.org/10.1038/s41598-025-88082-5 |
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