Evidence map›Paper›PMID 25232464›Full record

ArticleJournal of cancer science & therapy2014

TDP1/TOP1 Ratio as a Promising Indicator for the Response of Small Cell Lung Cancer to Topotecan.

Cornelia Meisenberg, Simon E Ward, Peter Schmid, Sherif F El-Khamisy

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

Article in Journal of cancer science & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

26 citing papers in PubMed, 36 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Cornelia MeisenbergThe Wellcome Trust DNA Repair Group, Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.
Simon E WardThe Sussex Translational Drug Discovery Group, University of Sussex, Brighton, UK.
Peter SchmidBrighton and Sussex Medical School, University of Sussex, Brighton, UK (former affiliation) ; Centre of Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University London, UK.
Sherif F El-KhamisyThe Wellcome Trust DNA Repair Group, Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK ; Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK ; Center of Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt.
Wellcome Trust · GB

Funding

Cancer Research UK 15349Wellcome Trust 091043
6 · The paper itself

Abstract

BACKGROUND AND

objectiveSmall cell lung cancer (SCLC) is one of the most challenging tumors to treat due to high proliferation rate, early metastatic dissemination and rapid development of chemotherapy resistance. The current treatment protocols involve the use of topoisomerase 1 (TOP1) poisons such as irinotecan and topotecan in combination with platinum-based compounds. TOP1 poisons kill cancer cells by trapping TOP1 on DNA, generating lethal DNA double-strand breaks. A potential mechanism employed by cancer cells to resist killing by TOP1 poisons is to overexpress enzymes involved in the repair of TOP1-DNA breaks. Tyrosyl DNA phosphodiesterase 1 (TDP1) is a key player in this process and despite its importance, no data is currently available to correlate TDP1 protein and mRNA levels with catalytic activity in SCLC. In addition, it is not known if TDP1 and TOP1 protein levels correlate with the cellular response of SCLC to TOP1 based therapies. METHODS AND

resultsWe report a remarkable variation in TDP1 and TOP1 protein levels in a panel of SCLC cell lines. TDP1 protein level correlates well with TDP1 mRNA and TDP1 catalytic activity, as measured by two newly developed independent activity assays, suggesting the potential utility of immunohistochemistry in assessing TDP1 levels in SCLC tissues. We further demonstrate that whilst TDP1 protein level alone does not correlate with topotecan sensitivity, TDP1/TOP1 ratio correlates well with sensitivity in 8 out of 10 cell lines examined.

conclusionThis study provides the first cellular analyses of TDP1 and TOP1 in SCLC and suggests the potential utility of TDP1/TOP1 ratio to assess the response of SCLC to topotecan. The establishment and validation of an easy-to-use TDP1 enzymatic assay in cell extracts could be exploited as a diagnostic tool in the clinic. These findings may help in stratifying patients that are likely to benefit from TOP1 poisons and TDP1 inhibitors currently under development.

Indexed as

Enzymatic assaySmall cell lung cancerTDP1 protein levelTOP1-DNATopotecan

Identifiers

PMID25232464
PMCPMC4163653
OpenAlexW2100789432

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.