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FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy.
https://repo.qst.go.jp/records/76892
https://repo.qst.go.jp/records/768924caac0ca-b7ed-4be6-93c0-bde8656934b0
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-09-24 | |||||
| タイトル | ||||||
| タイトル | FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Dewi Maulany Darwis, Narisa
× Dewi Maulany Darwis, Narisa× Nachankar, Ankita× Sasaki, Yasushi× Matsui, Toshiaki× Shin-ei, Noda× Murata, Kazutoshi× Tamaki, Tomoaki× Ando, Ken× Okonogi, Noriyuki× Shiba, Shintaro× Irie, Daisuke× Kaminuma, Takuya× Kumazawa, Takuya× Anakura, Mai× Yamashita, Souichi× Hirakawa, Takashi× Kakoti, Sangeeta× Hirota, Yuka× Tokino, Takashi× Iwase, Akira× Ohno, Tatsuya× Shibata, Atsushi× Oike, Takahiro× Nakano, Takashi× Murata, Kazutoshi× Tamaki, Tomoaki× Ando, Ken× Okonogi, Noriyuki× Shiba, Shintaro× Irie, Daisuke× Kaminuma, Takuya× Ohno, Tatsuya× Shibata, Atsushi× Nakano, Takashi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Radiotherapy is an essential component of cancer therapy. Carbon ion radiotherapy (CIRT) promises to improve outcomes compared with standard of care in many cancers. Nevertheless, clinicians often observe in-field recurrence after CIRT. This indicates the presence of a subset of cancers that harbor intrinsic resistance to CIRT. Thus, the development of methods to identify and sensitize CIRT-resistant cancers is needed. To address this issue, we analyzed a unique donor-matched pair of clinical specimens: a treatment-naïve tumor, and the tumor that recurred locally after CIRT in the same patient. Exon sequencing of 409 cancer-related genes identified enrichment of somatic mutations in and in the recurrent tumor compared with the treatment-naïve tumor, indicating a pivotal role for FGFR signaling in cancer cell survival through CIRT. Inhibition of FGFR using the clinically available pan-FGFR inhibitor LY2874455 sensitized multiple cancer cell lines to carbon ions at 3 Gy (RBE: relative biological effectiveness), the daily dose prescribed to the patient. The sensitizer enhancement ratio was 1.66 ± 0.17, 1.27 ± 0.09, and 1.20 ± 0.18 in A549, H1299, and H1703 cells, respectively. Our data indicate the potential usefulness of the analytical pipeline employed in this pilot study to identify targetable mutations associated with resistance to CIRT, and of LY21874455 as a sensitizer for CIRT-resistant cancers. The results warrant validation in larger cohorts. | |||||
| 書誌情報 |
International journal of molecular sciences 巻 20, 号 18, p. 4563-1, 発行日 2019-09 |
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| 出版者 | ||||||
| 出版者 | MDPI | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1422-0067 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 31540114 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3390/ijms20184563 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.mdpi.com/1422-0067/20/18/4563 | |||||
