Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity

Noriaki Tanaka, Abdullah A. Osman, Yoko Takahashi, Antje Lindemann, Ameeta A. Patel, Mei Zhao, Hideaki Takahashi, Jeffrey N. Myers

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Objectives: Currently there are no standard biomarkers of head and neck squamous cell carcinoma (HNSCC) response to therapy. This is, due to a lack of adequate predictive tumor models. To this end, we established cancer organoid lines from individual patient's tumors, and characterized their growth characteristics and response to different drug treatments with the objective of using these models for prediction of treatment response. Materials and Methods: Forty-three patients’ samples were processed to establish organoids. To analyze the character of these organoids, immunohistochemistry, Western blotting, drug sensitivity assays, clonogenic survival assays, and animal experiments were performed. The HPV status and TP53 mutational status were also confirmed in these lines. Results: HNSCC organoids were successfully established with success rate of 30.2%. Corresponding two-dimensional cell lines were established from HNSCC organoids at higher success rate (53.8%). These organoids showed similar histological features and stem cell, epithelial and mesenchymal marker expression to the original tumors, thus recapitulating many of the characteristics of the original tumor cells. The cisplatin and docetaxel IC50 were determined for HNSCC organoids and the corresponding 2D cell lines using drug sensitivity and clonogenic survival assays. Responses to drug treatment in vivo were found to be similar to the IC50 calculated from organoids by drug sensitivity assays in vitro. Conclusion: We established novel in vitro HNSCC cancer organoid lines retaining many properties of the original tumors from they were derived. These organoids can predict in vivo drug sensitivity and may represent useful tools to develop precision treatments for HNSCC.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalOral Oncology
Volume87
DOIs
StatePublished - Dec 2018

Keywords

  • 3D culture
  • Cancer organoid
  • Cancer tissue-originated spheroid (CTOS)
  • Cisplatin
  • Docetaxel
  • Drug sensitivity assay
  • HPV-positive
  • Head and neck cancer

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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