Evidence map›Paper›PMID 27259260›Full record

ArticleOncotarget2016

ATM protein is deficient in over 40% of lung adenocarcinomas.

Liza C Villaruz, Helen Jones, Sanja Dacic, Shira Abberbock, Brenda F Kurland, Laura P Stabile, Jill M Siegfried, Thomas P Conrads, Neil R Smith, Mark J O'Connor and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

33 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
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  9. Review
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  11. ATM Mutations Associate with Distinct Co-Mutational Patterns and Therapeutic Vulnerabilities in NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  12. Article
  13. Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  20. 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

12 authors at 5 institutions in 2 countries.

Liza C VillaruzUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Helen JonesAstrazeneca, Cambridge, United Kingdom.
Sanja DacicDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Shira AbberbockUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Brenda F KurlandUniversity of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Laura P StabileDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jill M SiegfriedDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Thomas P ConradsInova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA, USA.
Neil R SmithAstrazeneca, Cambridge, United Kingdom.
Mark J O'ConnorAstrazeneca, Cambridge, United Kingdom.
Andrew J PierceAstrazeneca, Cambridge, United Kingdom.
Christopher J BakkenistDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
AstraZeneca (United Kingdom) · GBUniversity of Pittsburgh · USUPMC Hillman Cancer Center · USInova Health System · USUniversity of Minnesota · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
Vitamin D3 Modulation of Inflammation and Lung Cancer RiskP50CA090440 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DACIC, SANJA · 2001 to 2015
$34.6M
NCI ET-CTN with Phase i Emphasis at UPCIUM1CA186690 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD, Farshid Dayyani · 2014 to 2026
$9.1M
Phase I Clinical Trials of Novel Anticancer AgentsU01CA099168 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHU, EDWARD · 2003 to 2013
$5.0M
Regulation of DNA replication fork progression by ATM kinase activityR01CA148644 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKKENIST, CHRISTOPHER J. · 2011 to 2015
$1.3M
NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA090440NCI NIH HHS R01 CA148644NCI NIH HHS U01 CA099168NCI NIH HHS UM1 CA186690
6 · The paper itself

Abstract

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

Indexed as

AdenocarcinomaAdenocarcinoma of LungAdultAgedAged, 80 and overAnimalsAtaxia Telangiectasia Mutated ProteinsCarcinoma, Non-Small-Cell LungCisplatinDNA DamageFemaleHumansImmunohistochemistryLung NeoplasmsMaleMiceAtaxia Telangiectasia Mutated ProteinsATM protein, humanATR protein, humanCisplatinataxia telangiectasia mutated (ATM)ATM and Rad-3-related (ATR)lung adenocarcinomanon-small cell lung cancer (NSCLC)

Identifiers

PMID27259260
PMCPMC5295384
OpenAlexW2414367793

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.