Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification

Rosemary Millen, Willem W B De Kort, Mandy Koomen, Gijs J F van Son, Roán Gobits, Bas Penning de Vries, Harry Begthel, Maurice Zandvliet, Patricia Doornaert, Cornelis P J Raaijmakers, Maarten H Geurts, Sjoerd G Elias, Robert J J van Es, Remco de Bree, Lot A Devriese, Stefan M Willems, Onno Kranenburg, Else Driehuis, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

17 Citations (Scopus)

Abstract

BACKGROUND: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas.

METHODS: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation.

FINDINGS: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC.

CONCLUSIONS: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation.

FUNDING: This work was funded by Oncode PoC 2018-P0003.

Original languageEnglish
Pages (from-to)290-310.e12
JournalMed (New York, N.Y.)
Volume4
Issue number5
DOIs
Publication statusPublished - 12 May 2023

Keywords

  • Humans
  • Head and Neck Neoplasms/drug therapy
  • Antineoplastic Agents/pharmacology
  • Carcinoma, Squamous Cell/drug therapy
  • Biomarkers/metabolism
  • Organoids/metabolism
  • Protein-Arginine N-Methyltransferases/metabolism

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