Evidence map›Paper›PMID 38086377›Full record

ArticleCell reports. Medicine2023

Protein signaling and drug target activation signatures to guide therapy prioritization: Therapeutic resistance and sensitivity in the I-SPY 2 Trial.

Rosa I Gallagher, Julia Wulfkuhle, Denise M Wolf, Lamorna Brown-Swigart, Christina Yau, Nicholas O'Grady, Amrita Basu, Ruixiao Lu, Michael J Campbell, Mark J Magbanua and 18 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01042379 (I-SPY Trial), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.8field-weighted citation impact, top 9% 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.

NCT01042379 phase2recruitingnot on this map

I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

TypeinterventionalSponsorQuantumLeap Healthcare CollaborativeRan2010 to 2031Enrolled5,000ConditionsBreast Neoplasms, Breast Cancer, Breast Tumors, AngiosarcomaArmsStandard Therapy, AMG 386 with or without Trastuzumab, AMG 479 (Ganitumab) plus Metformin, MK-2206 with or without Trastuzumab, AMG 386 and Trastuzumab
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Trial
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  4. Article
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  10. Laser capture microdissection.Nature reviews. Methods primers · 2025
    Article
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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 9 institutions in 1 country.

Rosa I GallagherCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA. Electronic address: rgallag3@gmu.edu.
Julia WulfkuhleCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA. Electronic address: jwulfkuh@gmu.edu.
Denise M WolfDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Lamorna Brown-SwigartDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Christina YauDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Nicholas O'GradyDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Amrita BasuDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Ruixiao LuQuantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA.
Michael J CampbellDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Mark J MagbanuaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Jean-Philippe CoppéDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
I-SPY 2 Investigators
Smita M AsareQuantum Leap Healthcare Collaborative, San Francisco, CA 94118, USA.
Laura SitDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Jeffrey B MatthewsDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Jane PerlmutterGemini Group, Ann Arbor, MI 48107, USA.
Nola HyltonDepartment of Radiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Minetta C LiuDepartment of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
W Fraser SymmansDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hope S RugoDivision of Hematology/Oncology, University of California, San Francisco, San Francisco, CA 94158, USA.
Claudine IsaacsLombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
Angela M DeMichelePerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Douglas YeeDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Paula R PohlmannDepartment of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gillian L HirstDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Laura J EssermanDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Laura J van 't VeerDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Emanuel F PetricoinCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA. Electronic address: epetrico@gmu.edu.
University of California, San Francisco · USGeorge Mason University · USQuantum Leap Healthcare Collaborative · USThe University of Texas MD Anderson Cancer Center · USGemini Computers (United States) · USGeorgetown University · USMayo Clinic in Arizona · USUniversity of Minnesota · USUniversity of Pennsylvania · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
The I SPY 2.2 TRIAL: Evolving to Imaging and Molecular Biomarker Response Directed Adaptive Sequential Treatment to Optimize Breast Cancer OutcomesP01CA210961 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nola M. Hylton-Watson · 2017 to 2026
$22.9M
Training SubprojectU54HG007990 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HAUSSLER, DAVID H, PATTERSON, DAVID · 2014 to 2018
$14.8M
The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trey Ideker, Nevan J Krogan · 2022 to 2026
$14.2M
Using Networks to Seed Hierarchical Whole-cell Models of CancerU54CA209891 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI IDEKER, TREY, KROGAN, NEVAN J · 2017 to 2021
$10.9M
NCI NIH HHS P01 CA210961NCI NIH HHS P30 CA082103NCI NIH HHS U54 CA209891NCI NIH HHS U54 CA274502NHGRI NIH HHS U54 HG007990
6 · The paper itself

Abstract

Molecular subtyping of breast cancer is based mostly on HR/HER2 and gene expression-based immune, DNA repair deficiency, and luminal signatures. We extend this description via functional protein pathway activation mapping using pre-treatment, quantitative expression data from 139 proteins/phosphoproteins from 736 patients across 8 treatment arms of the I-SPY 2 Trial (ClinicalTrials.gov: NCT01042379). We identify predictive fit-for-purpose, mechanism-of-action-based signatures and individual predictive protein biomarker candidates by evaluating associations with pathologic complete response. Elevated levels of cyclin D1, estrogen receptor alpha, and androgen receptor S650 associate with non-response and are biomarkers for global resistance. We uncover protein/phosphoprotein-based signatures that can be utilized both for molecularly rationalized therapeutic selection and for response prediction. We introduce a dichotomous HER2 activation response predictive signature for stratifying triple-negative breast cancer patients to either HER2 or immune checkpoint therapy response as a model for how protein activation signatures provide a different lens to view the molecular landscape of breast cancer and synergize with transcriptomic-defined signatures.

Indexed as

Drug Resistance, NeoplasmTriple Negative Breast NeoplasmsBiomarkersGene Expression ProfilingHumansNeoadjuvant TherapyBiomarkersbiomarkerbreast cancerclinical trialdrug targetLCMneoadjuvantphosphoproteinproteinresistanceRPPA

Identifiers

PMID38086377
PMCPMC10772394
OpenAlexW4389555398

What OpenQuestion holds

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Registered trials

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.