Evidence map›Paper›PMID 22287547›Full record

ArticleCancer research2012

PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma.

J Chad Brenner, Felix Y Feng, Sumin Han, Sonam Patel, Siddharth V Goyal, Laura M Bou-Maroun, Meilan Liu, Robert Lonigro, John R Prensner, Scott A Tomlins and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

172 citing papers in PubMed, 291 citations in OpenAlex.

  1. Trial
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  4. Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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112 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

J Chad BrennerMichigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Felix Y Feng
Sumin Han
Sonam Patel
Siddharth V Goyal
Laura M Bou-Maroun
Meilan Liu
Robert Lonigro
John R Prensner
Scott A Tomlins
Arul M Chinnaiyan
Howard Hughes Medical Institute · USUniversity of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · US

Funding

Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Howard Hughes Medical InstituteNCI NIH HHS T32 CA009676
6 · The paper itself

Abstract

Ewing's sarcoma family of tumors (ESFT) refers to aggressive malignancies which frequently harbor characteristic EWS-FLI1 or EWS-ERG genomic fusions. Here, we report that these fusion products interact with the DNA damage response protein and transcriptional coregulator PARP-1. ESFT cells, primary tumor xenografts, and tumor metastases were all highly sensitive to PARP1 inhibition. Addition of a PARP1 inhibitor to the second-line chemotherapeutic agent temozolamide resulted in complete responses of all treated tumors in an EWS-FLI1-driven mouse xenograft model of ESFT. Mechanistic investigations revealed that DNA damage induced by expression of EWS-FLI1 or EWS-ERG fusion genes was potentiated by PARP1 inhibition in ESFT cell lines. Notably, EWS-FLI1 fusion genes acted in a positive feedback loop to maintain the expression of PARP1, which was required for EWS-FLI-mediated transcription, thereby enforcing oncogene-dependent sensitivity to PARP-1 inhibition. Together, our findings offer a strong preclinical rationale to target the EWS-FLI1:PARP1 intersection as a therapeutic strategy to improve the treatment of ESFTs.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsAnimalsBone NeoplasmsCell Line, TumorHumansMiceOncogene Proteins, FusionPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingXenograft Model Antitumor AssaysEWS-FLI fusion proteinolaparibOncogene Proteins, FusionPARP1 protein, humanPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesProto-Oncogene Protein c-fli-1RNA-Binding Protein EWS

Identifiers

PMID22287547
PMCPMC3319786
OpenAlexW2144847112

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.