Evidence map›Paper›PMID 36207498›Full record

ArticleNPJ precision oncology2022

Pharmacometabolomics reveals urinary diacetylspermine as a biomarker of doxorubicin effectiveness in triple negative breast cancer.

Thomas J Velenosi, Kristopher W Krausz, Keisuke Hamada, Tiffany H Dorsey, Stefan Ambs, Shogo Takahashi, Frank J Gonzalez

Open access · goldAbstract read
In one paragraph

Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 14 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

7 authors at 1 institution in 2 countries.

Thomas J VelenosiLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA. thomas.velenosi@ubc.ca.ORCID http://orcid.org/0000-0001-7016-9037
Kristopher W KrauszLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
Keisuke HamadaLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
Tiffany H DorseyLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
Stefan AmbsLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7651-9309
Shogo TakahashiLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
Frank J GonzalezLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA. gonzalef@mail.nih.gov.ORCID http://orcid.org/0000-0002-7990-2140
National Institutes of Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) patients receive chemotherapy treatment, including doxorubicin, due to the lack of targeted therapies. Drug resistance is a major cause of treatment failure in TNBC and therefore, there is a need to identify biomarkers that determine effective drug response. A pharmacometabolomics study was performed using doxorubicin sensitive and resistant TNBC patient-derived xenograft (PDX) models to detect urinary metabolic biomarkers of treatment effectiveness. Evaluation of metabolite production was assessed by directly studying tumor levels in TNBC-PDX mice and human subjects. Metabolic flux leading to biomarker production was determined using stable isotope-labeled tracers in TNBC-PDX ex vivo tissue slices. Findings were validated in 12-h urine samples from control (n = 200), ER+/PR+ (n = 200), ER+/PR+/HER2+ (n = 36), HER2+ (n = 81) and TNBC (n = 200) subjects. Diacetylspermine was identified as a urine metabolite that robustly changed in response to effective doxorubicin treatment, which persisted after the final dose. Urine diacetylspermine was produced by the tumor and correlated with tumor volume. Ex vivo tumor slices revealed that doxorubicin directly increases diacetylspermine production by increasing tumor spermidine/spermine N

Identifiers

PMID36207498
PMCPMC9547066
OpenAlexW4303415331

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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.