Patient-derived head and neck cancer organoids recapitulate EGFR expression levels of respective tissues and are responsive to EGFR-targeted photodynamic therapy

Else Driehuis, Sacha Spelier, Irati Beltrán Hernández, Remco de Bree, Stefan M. Willems, Hans Clevers, Sabrina Oliveira

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are currently treated with surgery and/or radio-and chemotherapy. Despite these therapeutic interventions, 40% of patients relapse, urging the need for more effective therapies. In photodynamic therapy (PDT), a light-activated photosensitizer produces reactive oxygen species that ultimately lead to cell death. Targeted PDT, using a photosensitizer conjugated to tumor-targeting molecules, has been explored as a more selective cancer therapy. Organoids are self-organizing three-dimensional structures that can be grown from both normal and tumor patient-material and have recently shown translational potential. Here, we explore the potential of a recently described HNSCC–organoid model to evaluate Epidermal Growth Factor Receptor (EGFR)-targeted PDT, through either antibody-or nanobody-photosensitizer conjugates. We find that EGFR expression levels differ between organoids derived from different donors, and recapitulate EGFR expression levels of patient material. EGFR expression levels were found to correlate with the response to EGFR-targeted PDT. Importantly, organoids grown from surrounding normal tissues showed lower EGFR expression levels than their tumor counterparts, and were not affected by the treatment. In general, nanobody-targeted PDT was more effective than antibody-targeted PDT. Taken together, patient-derived HNSCC organoids are a useful 3D model for testing in vitro targeted PDT.

Original languageEnglish
Article number1880
JournalJournal of Clinical Medicine
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • EGFR
  • HNSCC
  • Organoids
  • Targeted photodynamic therapy

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