Evidence map›Paper›PMID 34359745›Full record

ArticleCancers2021

Targeted Mass Spectrometry Enables Quantification of Novel Pharmacodynamic Biomarkers of ATM Kinase Inhibition.

Jeffrey R Whiteaker, Tao Wang, Lei Zhao, Regine M Schoenherr, Jacob J Kennedy, Ulianna Voytovich, Richard G Ivey, Dongqing Huang, Chenwei Lin, Simona Colantonio and 18 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 13 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

28 authors at 4 institutions in 2 countries.

Jeffrey R WhiteakerFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.ORCID 0000-0001-5042-8580
Tao WangFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Lei ZhaoFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Regine M SchoenherrFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Jacob J KennedyFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Ulianna VoytovichFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Richard G IveyFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Dongqing HuangFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Chenwei LinFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Simona ColantonioCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Tessa W CaceresCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Rhonda R RobertsCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Joseph G KnottsCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Jan A KaczmarczykCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Josip BlonderCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Joshua J ReadingCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Christopher W RichardsonCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Stephen M HewittExperimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Sandra S Garcia-BuntleyCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
William BocikCancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Tara HiltkeOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
Henry RodriguezOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
Elizabeth A HarringtonTranslational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.
J Carl BarrettTranslational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.
Benedetta LombardiTranslational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.
Paola Marco-CasanovaTranslational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.
Andrew J PierceTranslational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.ORCID 0000-0001-9062-0307
Amanda G PaulovichFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
Frederick National Laboratory for Cancer Research · USFred Hutch Cancer Center · USAstraZeneca (United Kingdom) · GBNational Cancer Institute · US

Funding

Proteo-genomic Discovery, Prioritization and Verification of Cancer BiomarkersU24CA160034 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, PAULOVICH, AMANDA G · 2011 to 2016
$16.2M
Proteogenomic Studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefitU01CA214114 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BIRRER, MICHAEL, PAULOVICH, AMANDA G · 2017 to 2021
$8.4M
Clinical translation of a NexGen platform for quantifying protein networks in human biospecimensR01CA235575 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI AMANDA G PAULOVICH · 2019 to 2026
$6.0M
A proteomics research specialist in developing targeted mass spectrometry methods for quantifying proteins important in cancerR50CA211499 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Jeff Whiteaker · 2016 to 2026
$2.8M
NCI NIH HHS R01 CA235575NCI NIH HHS R01CA235575NCI NIH HHS R50 CA211499NCI NIH HHS R50CA211499NCI NIH HHS U01 CA214114NCI NIH HHS U01CA214114NCI NIH HHS U24 CA160034NCI NIH HHS U24CA160034Office of Research Infrastructure Programs, National Institutes of Health S10OD028685
6 · The paper itself

Abstract

The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.

Indexed as

DNA damage responseimmuno-MRMmultiple reaction monitoringtargeted proteomics

Identifiers

PMID34359745
PMCPMC8345163
OpenAlexW3187537469

What OpenQuestion holds

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LicenceCC BY
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.