Evidence map›Paper›PMID 32994807›Full record

ArticleTherapeutic advances in medical oncology2020

Exploiting DNA repair defects in triple negative breast cancer to improve cell killing.

Kevin J Lee, Elise Mann, Griffin Wright, Cortt G Piett, Zachary D Nagel, Natalie R Gassman

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

Article in Therapeutic advances in medical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
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  12. Novel Techniques for Mapping DNA Damage and Repair in the Brain.International journal of molecular sciences · 2024
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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

6 authors at 3 institutions in 1 country.

Kevin J LeeCollege of Medicine, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
Elise MannCollege of Medicine, University of South Alabama, Mobile, AL, USA.
Griffin WrightCollege of Medicine, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
Cortt G PiettHarvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Zachary D NagelHarvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Natalie R GassmanMitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36607, USA.
Harvard University · USUniversity of South Alabama · USUSA Mitchell Cancer Institute · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6M
NCI NIH HHS P01 CA092584
6 · The paper itself

Abstract

backgroundThe lack of molecular targets for triple negative breast cancer (TNBC) has limited treatment options and reduced survivorship. Identifying new molecular targets may help improve patient survival and decrease recurrence and metastasis. As DNA repair defects are prevalent in breast cancer, we evaluated the expression and repair capacities of DNA repair proteins in preclinical models.

methodsDNA repair capacity was analyzed in four TNBC cell lines, MDA-MB-157 (MDA-157), MDA-MB-231 (MDA-231), MDA-MB-468 (MDA-468), and HCC1806, using fluorescence multiplex host cell reactivation (FM-HCR) assays. Expression of DNA repair genes was analyzed with RNA-seq, and protein expression was evaluated with immunoblot. Responses to the combination of DNA damage response inhibitors and primary chemotherapy drugs doxorubicin or carboplatin were evaluated in the cell lines.

resultsDefects in base excision and nucleotide excision repair were observed in preclinical TNBC models. Gene expression analysis showed a limited correlation between these defects. Loss in protein expression was a better indicator of these DNA repair defects. Over-expression of PARP1, XRCC1, RPA, DDB1, and ERCC1 was observed in TNBC preclinical models, and likely contributed to altered sensitivity to chemotherapy and DNA damage response (DDR) inhibitors. Improved cell killing was achieved when primary therapy was combined with DDR inhibitors for ATM, ATR, or CHK1.

conclusionBase excision and nucleotide excision repair pathways may offer new molecular targets for TNBC. The functional status of DNA repair pathways should be considered when evaluating new therapies and may improve the targeting for primary and combination therapies with DDR inhibitors.

Indexed as

chemotherapyDNA damagehomologous recombinationnonhomologous end joiningnucleotide excision repairsmall molecule inhibitor

Identifiers

PMID32994807
PMCPMC7502856
OpenAlexW3087408276

What OpenQuestion holds

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LicenceCC BY-NC
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.