Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer
| Autor: | Becky A.S. Bibby, Ronnie Rodrigues Pereira, Ananya Choudhury, Kaye J. Williams, Elisabet More, Darragh G. McArt, Robert G. Bristow, Paul G. O’Reilly, N. Thiruthaneeswaran, Catharine M L West, Lingjian Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Radiation-Sensitizing Agents Urology 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Menadione DU145 SDG 3 - Good Health and Well-being Radioresistance Cell Line Tumor LNCaP Medicine Humans Clonogenic assay Hypoxia Manchester Cancer Research Centre business.industry United States Food and Drug Administration ResearchInstitutes_Networks_Beacons/mcrc Drug Repositioning Prostatic Neoplasms General Medicine Hypoxia (medical) medicine.disease Gemcitabine Diseases of the genitourinary system. Urology United States 030104 developmental biology Reproductive Medicine chemistry 030220 oncology & carcinogenesis Cancer research RC870-923 medicine.symptom business medicine.drug Research Article |
| Zdroj: | Bibby, B A S, Thiruthaneeswaran, N, Yang, L, Pereira, R R, More, E, McArt, D G, O'Reilly, P, Bristow, R G, Williams, K J, Choudhury, A & West, C M L 2021, ' Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer ', BMC urology, vol. 21, no. 1, 96 . https://doi.org/10.1186/s12894-021-00856-x BMC Urology Bibby, B A S, Thiruthaneeswaran, N, Yang, L, Pereira, R R, More, E, McArt, D G, O'Reilly, P, Bristow, R G, Williams, K J, Choudhury, A & West, C M L 2021, ' Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer ', BMC Urology, vol. 21, no. 1, pp. 96 . https://doi.org/10.1186/s12894-021-00856-x BMC Urology, Vol 21, Iss 1, Pp 1-11 (2021) |
| DOI: | 10.1186/s12894-021-00856-x |
| Popis: | Background The presence of hypoxia is a poor prognostic factor in prostate cancer and the hypoxic tumor microenvironment promotes radioresistance. There is potential for drug radiotherapy combinations to improve the therapeutic ratio. We aimed to investigate whether hypoxia-associated genes could be used to identify FDA approved drugs for repurposing for the treatment of hypoxic prostate cancer. Methods Hypoxia associated genes were identified and used in the connectivity mapping software QUADrATIC to identify FDA approved drugs as candidates for repurposing. Drugs identified were tested in vitro in prostate cancer cell lines (DU145, PC3, LNCAP). Cytotoxicity was investigated using the sulforhodamine B assay and radiosensitization using a clonogenic assay in normoxia and hypoxia. Results Menadione and gemcitabine had similar cytotoxicity in normoxia and hypoxia in all three cell lines. In DU145 cells, the radiation sensitizer enhancement ratio (SER) of menadione was 1.02 in normoxia and 1.15 in hypoxia. The SER of gemcitabine was 1.27 in normoxia and 1.09 in hypoxia. No radiosensitization was seen in PC3 cells. Conclusion Connectivity mapping can identify FDA approved drugs for potential repurposing that are linked to a radiobiologically relevant phenotype. Gemcitabine and menadione could be further investigated as potential radiosensitizers in prostate cancer. |
| Databáze: | OpenAIRE |
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