biostudies-literatureUm JHNational Research Foundation of Korea (NRF)NIDCR NIH HHSDivision of Diabetes, Endocrinology, and Metabolic DiseasesNational Institute of Dental and Craniofacial Research (NIDR)NIDDK NIH HHSCenter for Cancer Research (CCR)National Institute of Dental and Craniofacial ResearchNCI NIH HHSDivision of Diabetes, Endocrinology, and Metabolic Diseases (DEM)National Research Foundation of KoreaCenter for Cancer Research2726-2742https://www.ebi.ac.uk/biostudies/studies/S-EPMC12263324biostudies-literatureUnknown85(14)Head and neck squamous cell carcinoma (HNSCC) remains a significant health burden because of tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. In this study, we enrolled 31 patients with HNSCC for the establishment of patient-derived tumor organoids (PDO), which faithfully maintained the genomic features and histopathologic traits of the primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, with ex vivo drug sensitivity correlating with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor transcriptional heterogeneity (ITH) in PDOs, paraCancer researchGenomic and Single-Cell Analyses Characterize Patient-Derived Tumor Organoids to Enable Personalized Therapy for Head and Neck Squamous Cell Carcinoma.PMC122633241R01DE033648R37 CA237022R01 DE033648R37CA237022NRF-2021R1C1C10120041R01DK135562R01 DK135562Zheng YLin DCNam CMao QUm JHShin SJPark YMKoh YWZhao HfalseGenomic and Single-Cell Analyses Characterize Patient-Derived Tumor Organoids to Enable Personalized Therapy for Head and Neck Squamous Cell Carcinoma.Head and neck squamous cell carcinoma (HNSCC) remains a significant health burden because of tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. In this study, we enrolled 31 patients with HNSCC for the establishment of patient-derived tumor organoids (PDO), which faithfully maintained the genomic features and histopathologic traits of the primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, with ex vivo drug sensitivity correlating with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor transcriptional heterogeneity (ITH) in PDOs, para2025-01-01T00:00:00Z2025 Jul2026-06-12T05:20:14.424Z2026-06-12T03:08:03.844ZS-EPMC122633244026196310.1158/0008-5472.can-24-285010.1158/0008-5472.CAN-24-2850