Evidence map›Paper›PMID 31635359›Full record

ArticleCancers2019

Apalutamide Sensitizes Prostate Cancer to Ionizing Radiation via Inhibition of Non-Homologous End-Joining DNA Repair.

Wenhao Zhang, Chen-Yi Liao, Hajar Chtatou, Luca Incrocci, Dik C van Gent, Wytske M van Weerden, Julie Nonnekens

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Targeted Radionuclide Therapy: Current Landscape and Combination Approaches to Improve Oncology Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  9. Harnessing the Utility ofFrontiers in oncology · 2022
    Review
  10. Review
  11. Review
  12. AbirateroneFrontiers in oncology · 2021
    Article
  13. Article
  14. Article
  15. Article
  16. Article
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

7 authors at 2 institutions in 1 country.

Wenhao ZhangDepartment of Molecular Genetics, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. w.zhang@erasmusmc.nl.
Chen-Yi LiaoDepartment of Experimental Urology, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. c.liao@umail.leidenuniv.nl.
Hajar ChtatouDepartment of Experimental Urology, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. Hajarchtatou24@icloud.com.
Luca IncrocciDepartment of Radiation Oncology, Erasmus MC Cancer Institute, PO box 2040, 3000 CA Rotterdam, The Netherlands. l.incrocci@erasmusmc.nl.
Dik C van GentDepartment of Molecular Genetics, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. d.vangent@erasmusmc.nl.
Wytske M van WeerdenDepartment of Experimental Urology, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. w.vanweerden@erasmusmc.nl.ORCID 0000-0003-0324-4804
Julie NonnekensDepartment of Molecular Genetics, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands. j.nonnekens@erasmusmc.nl.
Erasmus MC · NLErasmus MC Cancer Institute · NL

Funding

Chinese Scholarship Council 201506270172Daniel den Hoed Foundation JNKWF Kankerbestrijding 10317KWF Kankerbestrijding EMCR 2014-7048
6 · The paper itself

Abstract

Androgen-deprivation therapy was shown to improve treatment outcome of external beam radiation therapy (EBRT) for locally advanced prostate cancer (PCa). DNA damage response (DDR) was suggested to play a role in the underlying mechanism, but conflicting results were reported. This study aims to reveal the role of the androgen receptor (AR) in EBRT-induced DDR and to investigate whether next-generation AR inhibitor apalutamide can radiosensitize PCa. PCa cell lines and tissue slices were treated with anti-androgen alone or combined with EBRT. The effect of treatments on cell growth, tissue viability, DDR, and cell cycle were investigated. RAD51 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) levels were determined by Western blotting. Homologous recombination (HR) capacity was measured with the directed repeats-green fluorescent protein (DR-GFP) assay. We report the radiosensitizing effect of anti-androgens, which showed synergism in combination with EBRT in AR-expressing tumor slices and cell lines. Moreover, a compromised DDR was observed in AR-expressing cells upon AR suppression. We found that AR inhibition downregulated DNA-PKcs expression, resulting in reduced non-homologous end-joining repair. DDR through HR was a secondary effect due to cell-cycle change. These data provide a mechanistic explanation for the combination regimen and support the clinical use of apalutamide together with EBRT for localized PCa patients.

Indexed as

anti-androgensapalutamideexternal beam radiation therapynon-homologous end-joiningprostate cancerradiosensitization

Identifiers

PMID31635359
PMCPMC6827010
OpenAlexW2981004493

What OpenQuestion 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 OpenQuestion graph.