Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancerCitation formats

  • External authors:
  • Becky A S Bibby
  • Niluja Thiruthaneeswaran
  • Lingjian Yang
  • Ronnie R Pereira
  • Elisabet More
  • Darragh G McArt
  • Paul O'Reilly

Standard

Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer. / Bibby, Becky A S; Thiruthaneeswaran, Niluja; Yang, Lingjian; Pereira, Ronnie R; More, Elisabet; McArt, Darragh G; O'Reilly, Paul; Bristow, Robert G; Williams, Kaye J; Choudhury, Ananya; West, Catharine M L.

In: BMC urology, Vol. 21, No. 1, 96, 01.07.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Bibby, BAS, Thiruthaneeswaran, N, Yang, L, Pereira, RR, More, E, McArt, DG, O'Reilly, P, Bristow, RG, Williams, KJ, Choudhury, A & West, CML 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

APA

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, 21(1), [96]. https://doi.org/10.1186/s12894-021-00856-x

Vancouver

Bibby BAS, Thiruthaneeswaran N, Yang L, Pereira RR, More E, McArt DG et al. Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer. BMC urology. 2021 Jul 1;21(1). 96. https://doi.org/10.1186/s12894-021-00856-x

Author

Bibby, Becky A S ; Thiruthaneeswaran, Niluja ; Yang, Lingjian ; Pereira, Ronnie R ; More, Elisabet ; McArt, Darragh G ; O'Reilly, Paul ; Bristow, Robert G ; Williams, Kaye J ; Choudhury, Ananya ; West, Catharine M L. / Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer. In: BMC urology. 2021 ; Vol. 21, No. 1.

Bibtex

@article{ec2e223520f84ea8aea2aa8da8c713a8,
title = "Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer",
abstract = "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.",
author = "Bibby, {Becky A S} and Niluja Thiruthaneeswaran and Lingjian Yang and Pereira, {Ronnie R} and Elisabet More and McArt, {Darragh G} and Paul O'Reilly and Bristow, {Robert G} and Williams, {Kaye J} and Ananya Choudhury and West, {Catharine M L}",
note = "Funding Information: This study was funded by the Cancer Research UK Manchester Centre (C147/A18083 and C147/A25254), Prostate Cancer UK (PG14-008-TR2) and the Movember Foundation as part of the Belfast-Manchester Centre of Excellence (CEO13-2-004). Professor Catharine West and Professor Ananya Choudhury are supported by the NIHR Manchester Biomedical Research Centre. The funding bodies were not involved in the concept, design, data analysis or preparation of manuscript. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jul,
day = "1",
doi = "10.1186/s12894-021-00856-x",
language = "English",
volume = "21",
journal = "BMC urology",
issn = "1471-2490",
publisher = "Springer Nature",
number = "1",

}

RIS

TY - JOUR

T1 - Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer

AU - Bibby, Becky A S

AU - Thiruthaneeswaran, Niluja

AU - Yang, Lingjian

AU - Pereira, Ronnie R

AU - More, Elisabet

AU - McArt, Darragh G

AU - O'Reilly, Paul

AU - Bristow, Robert G

AU - Williams, Kaye J

AU - Choudhury, Ananya

AU - West, Catharine M L

N1 - Funding Information: This study was funded by the Cancer Research UK Manchester Centre (C147/A18083 and C147/A25254), Prostate Cancer UK (PG14-008-TR2) and the Movember Foundation as part of the Belfast-Manchester Centre of Excellence (CEO13-2-004). Professor Catharine West and Professor Ananya Choudhury are supported by the NIHR Manchester Biomedical Research Centre. The funding bodies were not involved in the concept, design, data analysis or preparation of manuscript. Publisher Copyright: © 2021, The Author(s).

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

U2 - 10.1186/s12894-021-00856-x

DO - 10.1186/s12894-021-00856-x

M3 - Article

C2 - 34210300

VL - 21

JO - BMC urology

JF - BMC urology

SN - 1471-2490

IS - 1

M1 - 96

ER -