Evidence map›Paper›PMID 36644397›Full record

ArticleNAR cancer2023

ATR inhibition overcomes platinum tolerance associated with ERCC1- and p53-deficiency by inducing replication catastrophe.

Joshua R Heyza, Elmira Ekinci, Jacob Lindquist, Wen Lei, Christopher Yunker, Vilvanathan Vinothkumar, Rachelle Rowbotham, Lisa Polin, Natalie G Snider, Eric Van Buren and 8 more

Open access · goldAbstract read
In one paragraph

Article in NAR cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Embryonic Stem Cell-Specific Responses to DNA Replication Stress.bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024
    Review
  9. 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

18 authors at 2 institutions in 1 country.

Joshua R HeyzaDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Elmira EkinciDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Jacob LindquistDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Wen LeiDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Christopher YunkerDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Vilvanathan VinothkumarDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Rachelle RowbothamDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Lisa PolinDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Natalie G SniderDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.ORCID https://orcid.org/0000-0002-8693-5354
Eric Van BurenDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Donovan WatzaDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Jessica B BackDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Wei ChenDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Hirva MamdaniDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Ann G SchwartzDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
John J TurchiDepartments of Medicine and Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID https://orcid.org/0000-0001-5375-2992
Gerold BeplerDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Steve M PatrickDepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.ORCID https://orcid.org/0000-0003-3325-6750
Wayne State University · USNĒRx BioSciences (United States) · US

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI Julie Lynn Boerner · 1985 to 2026
$68.4M
Inflammation Pathways and COPD in the Development of Lung CancerR01CA141769 · NCI · WAYNE STATE UNIVERSITY · PI SCHWARTZ, ANN G. · 2011 to 2016
$8.7M
TRAINING PROGRAM IN THE BIOLOGY OF CANCERT32CA009531 · NCI · WAYNE STATE UNIVERSITY · PI Larry H Matherly · 1985 to 2026
$5.3M
Novel role of APOBEC3 enzymes as key mediators of cisplatin sensitivity through aberrant processing of interstrand crosslinksR01CA229535 · NCI · WAYNE STATE UNIVERSITY · PI PATRICK, STEVE M · 2019 to 2024
$2.0M
Targeting nucleotide excision repair in combination cancer therapyR01CA180710 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI TURCHI, JOHN J. · 2013 to 2017
$1.6M
A stable path for a core based scientist to advance imaging and cytometry in basic and preclinical research at the Karmanos Cancer InstituteR50CA251068 · NCI · WAYNE STATE UNIVERSITY · PI MOIN, KAMIAR · 2020 to 2024
$1.4M
NCI NIH HHS P30 CA022453NCI NIH HHS R01 CA141769NCI NIH HHS R01 CA180710NCI NIH HHS R01 CA229535NCI NIH HHS R50 CA251068NCI NIH HHS T32 CA009531
6 · The paper itself

Abstract

ERCC1/XPF is a heterodimeric DNA endonuclease critical for repair of certain chemotherapeutic agents. We recently identified that ERCC1- and p53-deficient lung cancer cells are tolerant to platinum-based chemotherapy. ATR inhibition synergistically re-stored platinum sensitivity to platinum tolerant ERCC1-deficient cells. Mechanistically we show this effect is reliant upon several functions of ATR including replication fork protection and altered cell cycle checkpoints. Utilizing an inhibitor of replication protein A (RPA), we further demonstrate that replication fork protection and RPA availability are critical for platinum-based drug tolerance. Dual treatment led to increased formation of DNA double strand breaks and was associated with chromosome pulverization. Combination treatment was also associated with increased micronuclei formation which were capable of being bound by the innate immunomodulatory factor, cGAS, suggesting that combination platinum and ATR inhibition may also enhance response to immunotherapy in ERCC1-deficient tumors.

Identifiers

PMID36644397
PMCPMC9832712
OpenAlexW4315642125

What OpenQuestion holds

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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.