Integrating artificial intelligence-driven digital pathology and genomics to establish patient-derived organoids as new approach methodologies for drug response in head and neck cancer

作者：Rose Doerfler, Jie Chen, Carl Kim, Joshua D. Smith, Micah Harris, Krishna B. Singh, Brian R. Isett, Rebekah Dadey, Daniel D. Brown, Adrian V. Lee, Xuefeng Wang, Matthew E. Spector, Seungwon Kim, Shaum Sridharan, Kevin J. Contrera, Katelyn Smith, Carly Reeder, Maureen A. Lyons, Jianhua Luo, Silvia Liu, Dan P. Zandberg, Heath D. Skinner, Ioannis K. Zervantonakis, Lazar Vujanović, Robert L. Ferris, Raja R. Seethala, José P. Zevallos, Jason J. Luke, Riyue Bao · 发表于：Oral Oncology · 年份：2025 · DOI：10.1016/j.oraloncology.2025.107742 · 被引用次数：11 · 研究领域：Cancer Cells and Metastasis、Cancer Genomics and Diagnostics、Mathematical Biology Tumor Growth

• PDO system models HPV-negative HNSCC across clinical and demographic backgrounds. • TransferNet-PDO, a novel AI tool, accurately classifies tumor vs. normal PDOs. • PDOs preserve clonal architecture and low-prevalence subclones over time. • PDOs reveal patient-specific drug responses to standard treatment and targeted therapies. • An integrated platform enables scalable precision oncology in HNSCC. Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor’s pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor versus normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs r...