دورية أكاديمية
Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer
| العنوان: | Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer |
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| المؤلفون: | 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 |
| المصدر: | 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-xTest |
| سنة النشر: | 2021 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | ResearchInstitutes_Networks_Beacons/mcrc, Manchester Cancer Research Centre |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/pdf |
| اللغة: | English |
| DOI: | 10.1186/s12894-021-00856-x |
| الإتاحة: | https://doi.org/10.1186/s12894-021-00856-xTest https://research.manchester.ac.uk/en/publications/ec2e2235-20f8-4ea8-aea2-aa8da8c713a8Test https://pure.manchester.ac.uk/ws/files/196449603/Manuscript_BMC_250521_final_BMCurology_clean.docxTest https://pure.manchester.ac.uk/ws/files/196449568/s12894_021_00856_x.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2FCA2A57 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12894-021-00856-x |
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