Evidence map›Paper›PMID 27728808›Full record

ArticleCancer cell2016

Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents - A Potential Therapy for Cancer.

Nidal E Muvarak, Khadiza Chowdhury, Limin Xia, Carine Robert, Eun Yong Choi, Yi Cai, Marina Bellani, Ying Zou, Zeba N Singh, Vu H Duong and 8 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

136 citing papers in PubMed, 207 citations in OpenAlex.

  1. Article
  2. Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  15. Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025
    Review
  16. Article
  17. Article
  18. Review
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  20. Article

76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 1 country.

Nidal E MuvarakDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Khadiza ChowdhuryDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Limin XiaThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Carine RobertDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Eun Yong ChoiDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Yi CaiThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Marina BellaniLaboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA.
Ying ZouDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zeba N SinghDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Vu H DuongDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Tyler RutherfordStevenson University, Stevenson, MD 21153, USA.
Pratik NagariaDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Søren M BentzenDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Michael M SeidmanLaboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA.
Maria R BaerDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA; Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Rena G LapidusDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Stephen B BaylinThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA; Van Andel Research Institute, Grand Rapids, MI 49503.
Feyruz V RassoolDepartment of Radiation Oncology, University of Maryland, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA. Electronic address: frassool@som.umaryland.edu.
University of Maryland, Baltimore · USUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterNational Institute on Aging · USSidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · USStevenson University · US

Funding

Repair of localized DNA damageZIAAG000746 · NIA · NATIONAL INSTITUTE ON AGING · PI SEIDMAN, MICHAEL · 2009 to 2025
$30.0M
Repair of localized DNA damageZ01AG000746 · NIA · NATIONAL INSTITUTE ON AGING · PI SEIDMAN, MICHAEL · 2007 to 2008
$607k
Inhibition of Pim kinases in acute myeloid leukemiaI01BX002184 · VA · BALTIMORE VA MEDICAL CENTER · PI BAER, MARIA R · 2015 to 2018
–
BLRD VA I01 BX002184Intramural NIH HHS Z01 AG000746Intramural NIH HHS ZIA AG000746
6 · The paper itself

Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites. This correlates with increased DNA damage, synergistic tumor cytotoxicity, blunting of self-renewal, and strong anti-tumor responses, in vivo in unfavorable AML subtypes and BRCA wild-type breast cancer cells. Our combinatorial approach introduces a strategy to enhance efficacy of PARPis in treating cancer.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorChromatinDNA Breaks, Double-StrandedDNA MethylationDrug SynergismFemaleHumansLeukemia, Myeloid, AcuteMaleMiceMice, Inbred NODMice, NudePhthalazinesPoly (ADP-Ribose) Polymerase-1ChromatinPARP1 protein, humanPhthalazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorstalazoparibAMLbreast cancerDNA damageDNA double-strand breakDNA repairDNMT1DNMT inhibitorPARPPARP inhibitorPARP trapping

Identifiers

PMID27728808
PMCPMC5201166
OpenAlexW2530874742

What OpenQuestion holds

Textmetadata
LicenceTDM
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.