Oral mucosal organoids as a potential platform for personalized cancer therapy
Driehuis, Else; Kolders, Sigrid; Spelier, Sacha; Lõhmussaar, Kadi; Willems, Stefan M.; Devriese, Lot A.; de Bree, Remco; de Ruiter, Emma J.; Korving, Jeroen; Begthel, Harry; van Es, Johan H.; Geurts, Veerle; He, Gui Wei; van Jaarsveld, Richard H.; Oka, Rurika; Muraro, Mauro J.; Vivié, Judith; Zandvliet, Maurice M.J.M.; Hendrickx, Antoni P.A.; Iakobachvili, Nino; Sridevi, Priya; Kranenburg, Onno; van Boxtel, Ruben; Kops, Geert J.P.L.; Tuveson, David A.; Peters, Peter J.; van Oudenaarden, Alexander; Clevers, Hans
(2019) Cancer Discovery, volume 9, issue 7, pp. 852 - 871
(Article)
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
... read more
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.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: Oncology, Journal Article
ISSN: 2159-8274
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: We thank Tulay Bayram for support regarding ethical regulatory affairs. We acknowledge Anneta Brousali, Petra van der Groep, Alexander Constantinides, and Anne Snelting of the Utrecht Platform for Organoid Technology (U-PORT; UMC Utrecht) for patient inclusion and tissue acquisition. We would like to thank the Molecular Diagnostics Department of the UMCU, Department of Pathology. Special thanks to Marja Blokland, Carmen Vooijs, and Wendy de Leng for help with targeted sequencing of the organoids. We thank Prashant Desai of John Hopkins University for contributing fluorescently labeled HSV virus. We thank Dohun Pyeon and Sharon Kuss-Duerkop of Michigan State University for contributing HPV16 virus, and for their guidance while setting up these infections. We would like to acknowledge the members of the Microscopy Core Lab at M4I Maastricht University for their scientific and technological support regarding high-pressure freezing and sample preparation for electron microscopy, with a special mention of Carmen López-Iglesias and Hans Duimel. We thank Yorick Post, Frans Schutgens, and Joep Beumer for critically reading this manuscript. This work was funded by the Oncode Institute (partly financed by the Dutch Cancer Society) and by the gravitation program Cancer GenomiCs.nl from the Netherlands Organization for Scientific Research (NWO) and a ZonMw grant (116.006.103). Research supported by an SU2C-DCS International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1213). Stand Up To Cancer (SU2C) is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. Funding Information: We thank Tulay Bayram for support regarding ethical regulatory affairs. We acknowledge Anneta Brousali, Petra van der Groep, Alexander Constantinides, and Anne Snelting of the Utrecht Platform for Organoid Technology (U-PORT; UMC Utrecht) for patient inclusion and tissue acquisition. We would like to thank the Molecular Diagnostics Department of the UMCU, Department of Pathology. Special thanks to Marja Blokland, Carmen Vooijs, and Wendy de Leng for help with targeted sequencing of the organoids. We thank Prashant Desai of John Hopkins University for contributing fluorescently labeled HSV virus. We thank Dohun Pyeon and Sharon Kuss-Duerkop of Michigan State University for contributing HPV16 virus, and for their guidance while setting up these infections. We would like to acknowledge the members of the Microscopy Core Lab at M4I Maastricht University for their scientific and technological support regarding high-pressure freezing and sample preparation for electron microscopy, with a special mention of Carmen López-Iglesias and Hans Duimel. We thank Yorick Post, Frans Schutgens, and Joep Beumer for critically reading this manuscript. This work was funded by the Oncode Institute (partly financed by the Dutch Cancer Society) and by the gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research (NWO) and a ZonMw grant (116.006.103). Research supported by an SU2C-DCS International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1213). Stand Up To Cancer (SU2C) is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. Publisher Copyright: © 2019 American Association for Cancer Research.
(Peer reviewed)