Evidence map›Paper›PMID 36980731›Full record

ArticleCancers2023

Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells.

Blue-Leaf A Cordes, Andrea Bilger, Richard J Kraus, Ella T Ward-Shaw, Madeline R Labott, Shinhyo Lee, Paul F Lambert, Janet E Mertz

Open access · goldFull text read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025
    Article
  3. Article
  4. Therapeutic opportunities in EBV-positive gastric cancer subtypes.Therapeutic advances in medical oncology · 2025
    Review
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

8 authors at 1 institution in 1 country.

Blue-Leaf A CordesMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Andrea BilgerMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0002-4838-4731
Richard J KrausMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Ella T Ward-ShawMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Madeline R LabottMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Shinhyo LeeMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Paul F LambertMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0001-7983-2755
Janet E MertzMcArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
Visualizing EBV and HCMV DNA Dynamics During InfectionP01CA022443 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI WILLIAM M. SUGDEN · 1985 to 2026
$53.1M
Defining Drivers of HPV-associated CarcinogenesisR35CA210807 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Paul F. Lambert · 2017 to 2026
$9.2M
NCI NIH HHS P01 CA022443NCI NIH HHS P30 CA014520NCI NIH HHS R35 CA210807NIH HHS P30 CA14520NIH HHS PO1 CA22443
6 · The paper itself

Abstract

Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV's latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we tested three classes of these drugs for preferential killing of the EBV-positive gastric cancer AGS-Akata cell line compared to its matched EBV-negative AGS control. We observed preferential killing with iron chelators [Deferoxamine (DFO); Deferasirox (DFX)] and a prolyl hydroxylase inhibitor (BAY 85-3934 (Molidustat)), but not with a neddylation inhibitor [MLN4924 (Pevonedistat)]. DFO and DFX also induced preferential killing of the EBV-positive gastric cancer AGS-BDneo and SNU-719 cell lines. Preferential killing was enhanced when low-dose DFX (10 μM) was combined with the antiviral prodrug ganciclovir. DFO and DFX induced lytic EBV reactivation in approximately 10% of SNU-719 and 20-30% of AGS-Akata and AGS-BDneo cells. However, neither DFO nor DFX significantly induced synthesis of lytic EBV proteins in xenografts grown in NSG mice from AGS-Akata cells above the level observed in control-treated mice. Therefore, these FDA-approved iron chelators are less effective than gemcitabine at promoting EBV reactivation in vivo despite their high specificity and efficiency in vitro.

Indexed as

deferasiroxdeferoxamineEBVgastric cancerlytic-induction therapy

Identifiers

PMID36980731
PMCPMC10046841
OpenAlexW4327969884

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read88
identifiers read2
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.