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Updated: May 8, 2026

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A Head and Neck Cancer Patient-Specific Microphysiological System for Predicting Response to Chemoradiation.

Adeel Ahmed1, Nathan Hendrikse1, Rene Welch Schwartz2

  • 1Carbone Cancer Center, University of Wisconsin - Madison, Madison, WI, USA.

Biorxiv : the Preprint Server for Biology
|May 7, 2026
PubMed
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A novel patient-specific microphysiological system (MPS) models head and neck cancer (HNC) tumor microenvironments. This system accurately predicts treatment response, offering a functional tool for personalized HNC therapy.

Area of Science:

  • Oncology
  • Biotechnology
  • Cancer Research

Background:

  • Head and neck cancer (HNC) is a prevalent malignancy with high recurrence rates.
  • Current predictive models for HNC treatment response lack patient-specific complexity and tumor microenvironment (TME) representation.
  • Chemoradiation is standard care, but predicting individual patient response remains challenging.

Purpose of the Study:

  • To develop and validate a patient-specific microphysiological system (MPS) for reconstructing the HNC TME.
  • To assess the MPS's ability to model HNC biology, including hypoxia and radiation response.
  • To identify functional metrics within the MPS that predict therapeutic response and clinical outcomes.

Main Methods:

  • Constructed a vascularized 3D MPS using patient-derived HNC cells, fibroblasts, and immune cells within a hydrogel.

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  • Utilized single-cell RNA sequencing to confirm preservation of cellular heterogeneity.
  • Employed compartment-resolved imaging and spheroid analysis to monitor treatment dynamics.
  • Main Results:

    • The MPS successfully recapitulated HNC TME characteristics, including tumor hypoxia and altered radiation response.
    • Patient-specific MPS demonstrated divergent responses to chemoradiation, reflecting clinical heterogeneity.
    • The rate of spheroid area change during treatment correlated with tumor recurrence, indicating predictive potential.

    Conclusions:

    • The patient-specific MPS is a viable platform for modeling HNC TME and predicting chemoradiation response.
    • This system offers a functional tool to overcome limitations of current predictive models for HNC.
    • Spheroid area change dynamics in the MPS may serve as a novel biomarker for HNC therapeutic response and recurrence.