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Cited by 408Cancer Cells and MetastasisHead and Neck Cancer Studies3D Printing in Biomedical Research

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

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Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lõhmussaar, Kadi, Willems, Stefan M., Devriese, Lot A., de Bree, Remco, de Ruiter, Emma J. +20 more·2019·Cancer Discovery
DOI 10.1158/2159-8290.cd-18-1522

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Abstract

Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)–derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. Significance: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice. See related commentary by Hill and D'Andrea, p. 828. This article is highlighted in the In This Issue feature, p. 813

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Authors
Driehuis, E., Kolders, S., Spelier, S., Lõhmussaar, K., Willems, S. M., Devriese, L. A., de Bree, R., de Ruiter, E. J., Korving, J., Begthel, H., van Es, J. H., Geurts, V., He, G.-W., van Jaarsveld, R. H., Oka, R., Muraro, M. J., Vivié, J., Zandvliet, M. M. J. M., Hendrickx, A. P. A., Iakobachvili, N., Sridevi, P., Kranenburg, O., van Boxtel, R., Kops, G. J. P. L., Tuveson, D. A., Peters, P. J., van Oudenaarden, A., & Clevers, H.
Affiliations
  • Royal Netherlands Academy of Arts and Sciences (NL)
  • University Medical Center Utrecht (NL)
  • 4Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 2Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 1Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, the Netherlands.
  • Princess Máxima Center (NL)
  • Utrecht University (NL)
  • Maastricht University (NL)
  • Cold Spring Harbor Laboratory (US)
  • 5Princess Maxima Center, Utrecht, the Netherlands.
Corresponding author
Clevers, Hans
ORCID
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2019-07-01
Volume
9
Issue
7
Pages
852-871
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-18-1522
OpenAlex
W2943439515
Cited by
408
References
10
Citations by year
2026: 50 · 2025: 51 · 2024: 82 · 2023: 53 · 2022: 57 · 2021: 62 · 2020: 45 · 2019: 5 · 2018: 1
FWCI
17.66
Type
journal article
Language
en
Update notices
correction (2020-03-03)
Open access
Locations
  • Cancer Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
Funders
Stand Up To Cancer (SU2C-AACR-DT1213)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
head and neck squamous cell carcinoma, tumor organoids, organoid culture, xenotransplantation, drug screening, cisplatin, carboplatin, cetuximab, radiotherapy, targeted therapy, precision oncology
MeSH terms
Cetuximab, Squamous Cell Carcinoma of Head and Neck, Animals, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Drug Screening Assays, Antitumor, Head and Neck Neoplasms, Humans, Mouth Mucosa, Organoids, Carboplatin, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Mice, Precision Medicine, Chemoradiotherapy

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