Expanding roles of cell cycle checkpoint inhibitors in radiation oncology
| Autor: | Adrian Eek Mariampillai, Lilli T. E. Bay, Sissel Hauge, Randi G. Syljuåsen, Helga B. Landsverk, Gro Elise Rødland |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell cycle checkpoint
Radiological and Ultrasound Technology biology Kinase DNA damage 030218 nuclear medicine & medical imaging Cell biology 03 medical and health sciences Wee1 0302 clinical medicine Key factors 030220 oncology & carcinogenesis Radiation oncology biology.protein Radiology Nuclear Medicine and imaging biological phenomena cell phenomena and immunity |
| Zdroj: | International Journal of Radiation Biology. 99:941-950 |
| ISSN: | 1362-3095 0955-3002 |
| DOI: | 10.1080/09553002.2021.1913529 |
| Popis: | Radiation-induced activation of cell cycle checkpoints have been of long-standing interest. The WEE1, CHK1 and ATR kinases are key factors in cell cycle checkpoint regulation and are essential for the S and G2 checkpoints. Here, we review the rationale for why inhibitors of WEE1, CHK1 and ATR could be beneficial in combination with radiation.Combined treatment with radiation and inhibitors of these kinases results in checkpoint abrogation and subsequent mitotic catastrophe. This might selectively radiosensitize tumor cells, as they often lack the p53-dependent G1 checkpoint and therefore rely more on the G2 checkpoint to repair DNA damage. Further affecting the repair of radiation damage, inhibition of WEE1, CHK1 or ATR also specifically suppresses the homologous recombination repair pathway. Moreover, inhibition of these kinases can induce massive replication stress during S phase of the cell cycle, likely contributing to eliminate radioresistant S phase cells. Intriguingly, recent findings suggest that cell cycle checkpoint inhibitors in combination with radiation can also enhance anti-tumor immune effects. Altogether, the expanding knowledge about the functional roles of WEE1, CHK1 and ATR inhibitors support that they are promising candidates for use in combination with radiation treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|