@article{oai:repo.qst.go.jp:00076892,
 author = {Dewi Maulany Darwis, Narisa and Nachankar, Ankita and Sasaki, Yasushi and Matsui, Toshiaki and Shin-ei, Noda and Murata, Kazutoshi and Tamaki, Tomoaki and Ando, Ken and Okonogi, Noriyuki and Shiba, Shintaro and Irie, Daisuke and Kaminuma, Takuya and Kumazawa, Takuya and Anakura, Mai and Yamashita, Souichi and Hirakawa, Takashi and Kakoti, Sangeeta and Hirota, Yuka and Tokino, Takashi and Iwase, Akira and Ohno, Tatsuya and Shibata, Atsushi and Oike, Takahiro and Nakano, Takashi and Murata, Kazutoshi and Tamaki, Tomoaki and Ando, Ken and Okonogi, Noriyuki and Shiba, Shintaro and Irie, Daisuke and Kaminuma, Takuya and Ohno, Tatsuya and Shibata, Atsushi and Nakano, Takashi},
 issue = {18},
 journal = {International journal of molecular sciences},
 month = {Sep},
 note = {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.},
 title = {FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy.},
 volume = {20},
 year = {2019}
}