Evidence map›Paper›PMID 34210300›Full record

ArticleBMC urology2021

Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer.

Becky A S Bibby, Niluja Thiruthaneeswaran, Lingjian Yang, Ronnie R Pereira, Elisabet More, Darragh G McArt, Paul O'Reilly, Robert G Bristow, Kaye J Williams, Ananya Choudhury and 1 more

Open access · goldAbstract read
In one paragraph

Article in BMC urology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Becky A S Bibby *Translational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Niluja Thiruthaneeswaran *Translational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. nilujat@ausdoctors.net.ORCID http://orcid.org/0000-0002-0253-0895
Lingjian YangTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Ronnie R PereiraTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Elisabet MoreTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Darragh G McArtCentre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
Paul O'ReillyCentre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
Robert G BristowTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Kaye J WilliamsSchool of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK.
Ananya ChoudhuryTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Catharine M L WestTranslational Radiobiology Group, Division of Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Manchester Academic Health Science Centre · GBQueen's University Belfast · GBThe University of Sydney · AUUniversity of Manchester · GB

Funding

Cancer Research UK C147/A18083PCUK PG14-008-TR2
6 · The paper itself

Abstract

backgroundThe 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.

methodsHypoxia 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.

resultsMenadione 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.

conclusionConnectivity 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.

Indexed as

Drug RepositioningRadiation-Sensitizing AgentsCell Line, TumorHumansHypoxiaMaleProstatic NeoplasmsUnited StatesUnited States Food and Drug AdministrationRadiation-Sensitizing Agents

Identifiers

PMID34210300
PMCPMC8247203
OpenAlexW3175551773

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.