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Publications

Journal Article Epublish

PubMed: 40624315 DOI: 10.1038/s41598-025-88082-5

Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses.

Sci Rep 15(1):24221

Authors: 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

Affiliations

  • 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.
  • Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.
  • 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.
  • Department of Surgery, Section of Otolaryngology/Head and Neck Surgery, Aga Khan University, Karachi, 74800, Pakistan.
  • Division of Otolaryngology/Head and Neck Surgery, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
  • Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Pancreatic Cancer Center, Henry Ford Health, Detroit, MI, 48202, USA.
  • Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
  • Department of Medicine, Computational Biomedicine Section, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, 02118, USA.
  • Bioinformatics Program, Faculty of Computing and Data Science , Boston University, Boston, MA, 02215, USA.
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Department of Otolaryngology/Head and Neck Surgery, Harvard Medical School, Boston, MA, 02115, USA.
  • 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.

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.

MeSH

Cells, Pharmaceutical Preparations, Neoplasms, Drug Therapy, Squamous Cell Carcinoma Of Head And Neck, Organoids, Natural Science Disciplines, Therapeutics, Mutation, Chemotherapy