Abstract B023: Patient-specific, organotypic head and neck cancer model for personalized medicine
Authors: Adeel Ahmed, Nathan W Hendrikse, Marcos A Lares, Fauzan Ahmed, Adam R Burr, Paul M Harari, David J Beebe, Sheena C Kerr
Journal: Cancer Research (2025)

Abstract Background: Head and neck cancer (HNC) treatment outcomes are highly variable among patients, and lack of actionable data on individual treatment responses limits effective clinical decision-making. Microphysiological systems (MPS) are advanced in vitro models that replicate the biological, physical, and functional properties of human tissues, offering a promising approach to testing treatment responses in vitro. Despite their potential, MPS adoption for evaluating standard clinical treatments—such as radiation and chemotherapy—has been hindered by the challenge of recreating the complexity of the tumor microenvironment. To address this, we developed an HNC MPS that mimics patient-specific tumor microenvironments using primary cells from patient tumors embedded in a 3D matrix with vascular components. This model was used to evaluate individualized responses to radiation and chemotherapy through cell-scale readouts, including DNA damage, proliferation, and migration. Methods: The HNC MPS comprises a microscale chamber containing two removable rods. A collagen-fibronectin matrix incorporating patient-derived tumor spheroids, fibroblasts, and immune cells was cast in the chamber. The matrix polymerized around the removable rods, which were subsequently extracted to create molded luminal structures. These lumens were lined with vascular and lymphatic endothelial cells to recreate a vascularized tumor microenvironment. An optimized media formulation supported the growth of all cell types within the MPS. The model was treated with radiation, cisplatin, or both to simulate the current standard of care. Cellular responses, including viability, proliferation, migration, and DNA damage, were assessed using immunofluorescence and cytokine secretion. A custom image processing pipeline analyzed multiple orthogonal readouts to reveal treatment responses at the cellular level with metrics to compare to actual patient outcomes under development. The model was further validated by comparing it with tumor tissue using single-cell RNA sequencing (scRNA-seq). Experiments were conducted with samples from multiple patients. Results: We successfully developed a patient-specific model of the HNC microenvironment using primary cells isolated from patient tumor tissue. This model captured key patient-specific features, such as angiogenesis and cell migration, and provided insights into treatment responses across different modalities. Cellular responses, such as proliferation and migration, were quantified, and scRNA-seq demonstrated close concordance between the MPS and patient tumor tissue. Our model presents a valuable functional assay for predicting patient-specific responses to therapy and validating biomarkers for treatment stratification. Conclusion: The HNC MPS is a robust in vitro platform that recapitulates patient-specific tumor microenvironments and treatment responses. It offers a promising approach for personalized cancer therapy, enabling functional assays to guide clinical decision-making and improve treatment outcomes for patients with HNC. Citation Format: Adeel Ahmed, Nathan W Hendrikse, Marcos A Lares, Fauzan Ahmed, Adam R Burr, Paul M Harari, David J Beebe, Sheena C Kerr. Patient-specific, organotypic head and neck cancer model for personalized medicine [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B023.