Evidence map›Paper›PMID 34671754›Full record

ArticleCell reports methods2021

Targeted mass spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP Kinase, and AKT signaling.

Jeffrey R Whiteaker, Kanika Sharma, Melissa A Hoffman, Eric Kuhn, Lei Zhao, Alexandra R Cocco, Regine M Schoenherr, Jacob J Kennedy, Ulianna Voytovich, Chenwei Lin and 14 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports methods, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Direct Comparison of MRM-MS and PRM-MS Methods for Quantitative Ganglioside Analysis.Journal of the American Society for Mass Spectrometry · 2026
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  12. An Introduction to Advanced Targeted Acquisition Methods.Molecular & cellular proteomics : MCP · 2021
    Review
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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

24 authors at 9 institutions in 1 country.

Jeffrey R WhiteakerClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Kanika SharmaNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Melissa A HoffmanProteomics and Metabolomics Core, Department of Molecular Oncology, and Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Eric KuhnBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Lei ZhaoClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Alexandra R CoccoGillings School of Global Public Health, Kenan-Flagler Business School, University of North Carolina, Chapel Hill, NC 27599, USA.
Regine M SchoenherrClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Jacob J KennedyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Ulianna VoytovichClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Chenwei LinClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bin FangProteomics and Metabolomics Core, Department of Molecular Oncology, and Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Kiah BowersProteomics and Metabolomics Core, Department of Molecular Oncology, and Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Gordon WhiteleyAntibody Characterization Laboratory, Leidos Biochemical Research Inc, Frederick National Laboratory for Cancer Research ATRF, Frederick, MD 21701, USA.
Simona ColantonioAntibody Characterization Laboratory, Leidos Biochemical Research Inc, Frederick National Laboratory for Cancer Research ATRF, Frederick, MD 21701, USA.
William BocikAntibody Characterization Laboratory, Leidos Biochemical Research Inc, Frederick National Laboratory for Cancer Research ATRF, Frederick, MD 21701, USA.
Rhonda RobertsAntibody Characterization Laboratory, Leidos Biochemical Research Inc, Frederick National Laboratory for Cancer Research ATRF, Frederick, MD 21701, USA.
Tara HiltkeOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Emily BojaOffice 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.
Frank McCormickNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Matthew HolderfieldNCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Steven A CarrBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
John M KoomenProteomics and Metabolomics Core, Department of Molecular Oncology, and Department of Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Amanda G PaulovichClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Fred Hutch Cancer Center · USLeidos (United States) · USMoffitt Cancer Center · USNational Cancer Institute · USBroad Institute · USFrederick National Laboratory for Cancer Research · USRevolution Medicines (United States) · USUniversity of California, San Francisco · USUniversity of North Carolina at Chapel Hill · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
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
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
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS P30 CA076292NCI NIH HHS R50 CA211499NCI NIH HHS U01 CA214114NCI NIH HHS U24 CA160034
6 · The paper itself

Abstract

summaryA primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX-4720. These assays replace over 60 Western blots with quantitative mass spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism of action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov. MOTIVATION: A lack of quantitative, multiplexable assays for phosphosignaling limits comprehensive investigation of aberrant signaling in cancer and evaluation of novel treatments. To alleviate this limitation, we sought to develop assays using targeted mass spectrometry for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. The resulting assays provide a resource for replacing over 60 Western blots in examining cancer signaling and tumor biology with high molecular specificity and quantitative rigor.

Indexed as

MelanomaProto-Oncogene Proteins c-aktHumansMass SpectrometryMitogen-Activated Protein Kinase KinasesReceptor Protein-Tyrosine KinasesTyrosineMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesTyrosineAKTassay resourceCancer signalingimmuno-MRMMAP kinasepharmacodynamicsquantitative proteomicsRASRTKtargeted therapy

Identifiers

PMID34671754
PMCPMC8525888
OpenAlexW3166347940

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.