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Radiosensitization by the Selective Pan-FGFR Inhibitor LY2874455
Narisa Dewi Maulany Darwis1,2, Eisuke Horigome1, Shan Li1
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi 371-8511, Gunma, Japan.
Cells
|June 10, 2022
Summary
The selective pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor LY2874455 enhances cancer cell radiosensitivity. This drug combination shows promise for improving radiation therapy outcomes.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Targeted Therapy
Background:
- Ionizing radiation triggers cancer cell cytoprotective pathways.
- Fibroblast Growth Factor Receptor (FGFR) signaling is implicated in these protective mechanisms.
- Targeting FGFR is a strategy to enhance radiosensitivity.
Purpose of the Study:
- To investigate the radiosensitizing effects of LY2874455, a selective pan-FGFR inhibitor.
- To evaluate the efficacy of LY2874455 in combination with X-rays in radioresistant human cancer cell lines and xenografts.
Main Methods:
- Utilized radioresistant human cancer cell lines (H1703, A549, H1299).
- Assessed radiosensitization by measuring clonogenic survival after X-ray exposure combined with LY2874455.
- Evaluated tumor growth suppression in A549 xenografts treated with combination therapy.
Main Results:
- LY2874455 significantly increased the radiosensitivity of H1703, A549, and H1299 cells (31%-62%).
- Combination treatment induced mitotic catastrophe, a marker of radiation-induced cell death.
- LY2874455 and X-ray combination therapy markedly suppressed A549 xenograft growth without significant toxicity.
Conclusions:
- This study demonstrates the radiosensitizing potential of the selective pan-FGFR inhibitor LY2874455.
- Combination therapy with LY2874455 and radiation warrants further clinical investigation for cancer treatment.
