Oral mucosal organoids as a potential platform for personalized cancer therapy

Else Driehuis, Sigrid Kolders, Sacha Spelier, Kadi Lõhmussaar, Stefan M. Willems, Lot A. Devriese, Remco de Bree, Emma J. de Ruiter, Jeroen Korving, Harry Begthel, Johan H. van Es, Veerle Geurts, Gui-Wei He, Richard H. van Jaarsveld, Rurika Oka, Mauro J. Muraro, Judith Vivié, Maurice M.J.M. Zandvliet, Antoni P.A. Hendrickx, Nino Iakobachvili, Priya Sridevi, Onno Kranenburg, Ruben van Boxtel, Geert J.P.L. Kops, David A. Tuveson, Peter J. Peters, Alexander van Oudenaarden and Hans Clevers

Published: 01/07/2019


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.

Full Access Link: Cancer Discovery