Radiosensitization by the Selective Pan-FGFR Inhibitor LY2874455

Narisa Dewi Maulany Darwis, Eisuke Horigome, Shan Li, Akiko Adachi, Takahiro Oike, Atsushi Shibata, Yuka Hirota, Tatsuya Ohno

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Ionizing radiation activates cytoprotective pathways in cancer cells. Fibroblast growth factor receptor (FGFR) is a key player in these pathways. Thus, FGFR signaling is a potential target to induce radiosensitization. LY2874455 is an orally administrable selective pan-FGFR inhibitor. However, the radiosensitizing effects of LY2874455 remain unclear. In this study, we addressed this issue by using radioresistant human cancer cell lines H1703 (FGFR1 mutant), A549 (FGFR1–4 wild-type), and H1299 (FGFR1–4 wild-type). At an X-ray dose corresponding to 50%-clonogenic survival as the endpoint, 100 nM LY2874455 increased the sensitivity of H1703, A549, and H1299 cells by 31%, 62%, and 53%, respectively. The combination of X-rays and LY2874455 led to a marked induction of mitotic catastrophe, a hallmark of radiation-induced cell death. Furthermore, combination treatment suppressed the growth of A549 xenografts to a significantly greater extent than either X-rays or the drug alone without noticeable toxicity. This is the first report to show the radiosensitizing effect of a selective pan-FGFR inhibitor. These data suggest the potential efficacy of LY2874455 as a radiosensitizer, warranting clinical validation.

Original languageEnglish
Article number1727
JournalCells
Volume11
Issue number11
DOIs
Publication statusPublished - 2022 Jun 1
Externally publishedYes

Keywords

  • cancer
  • FGFR
  • LY2874455
  • radiosensitization
  • radiotherapy

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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