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Drug screening with a novel tumor-derived cell line identified alternative therapeutic options for patients with atypical teratoid/rhabdoid tumor

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Abstract

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare intracranial tumor occurring predominantly in young children. The prognosis is poor, and no effective treatment is currently available. To develop novel effective therapies, there is a need for experimental models for AT/RT. In this research, we established a cell line from a patient’s AT/RT tissue (designated ATRT_OCGH) and performed drug screening using 164 FDA-approved anti-cancer agents, to identify candidates for therapeutic options. We found that bortezomib, a proteasome inhibitor, was among the agents for which the cell line showed high sensitivity, along with tyrosine kinase inhibitors, topoisomerase inhibitors, and histone deacetylase inhibitors, which are known to exert anti-AT/RT effects. Concomitant use of panobinostat potentiated the inhibitory effect of bortezomib on AT/RT cell proliferation. Our findings may provide a rationale for considering combination therapy of panobinostat and bortezomib for treatment of AT/RT.

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Acknowledgements

The authors thank the patient and their family for participating in this research. We thank Y. Matsushita and K. Hatake for their technical support.

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Author notes

  1. Yoshiko Nakano and Mutsumi Takadera contributed equally.

Authors and Affiliations

  1. Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yoshiko Nakano, Mutsumi Takadera, Makoto Miyazaki, Yui Kimura, Tatsuya Ozawa & Koichi Ichimura

  2. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Yoshiko Nakano, Yuki Okuhiro, Kai Yamasaki & Junichi Hara

  3. Department of Neurosurgery, Yokohama City University, Yokohama, Japan

    Mutsumi Takadera

  4. Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan

    Makoto Miyazaki

  5. Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan

    Zhiwei Qiao, Kosei Nakajima, Rei Noguchi & Tadashi Kondo

  6. Department of Innovative Seeds Evaluation, National Cancer Center Research Institute, Tokyo, Japan

    Rieko Oyama

  7. Department of Pediatric Neurosurgery, Osaka City General Hospital, Osaka, Japan

    Noritsugu Kunihiro

  8. Department of Pathology, Osaka City General Hospital, Osaka, Japan

    Hiroko Fukushima & Takeshi Inoue

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  1. Yoshiko Nakano
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  2. Mutsumi Takadera
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  15. Tatsuya Ozawa
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  17. Koichi Ichimura
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Corresponding author

Correspondence to Yoshiko Nakano.

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The authors declare that they have no conflicts of interest.

Ethics approval

The study was approved by the Institutional Review Boards at all participating institutions.

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Informed, written consent was obtained from the patient’s parent.

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Nakano, Y., Takadera, M., Miyazaki, M. et al. Drug screening with a novel tumor-derived cell line identified alternative therapeutic options for patients with atypical teratoid/rhabdoid tumor. Human Cell 34, 271–278 (2021). https://doi.org/10.1007/s13577-020-00438-3

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  • DOI: https://doi.org/10.1007/s13577-020-00438-3

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