ArticleCancer research2018
Mass Spectrometry-Based Proteomics Reveals Potential Roles of NEK9 and MAP2K4 in Resistance to PI3K Inhibition in Triple-Negative Breast Cancers.
Open access · bronzeAbstract read
In one paragraph
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.2field-weighted citation impact, top 6% of its field
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.
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.
Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- Proteomic approaches for interrogating kinase signaling networks.The Journal of investigative dermatology · 2026Article
- Integrative Proteogenomics and Forward Genetics Reveal a Novel Mitotic Vulnerability in Triple-Negative Breast Cancer.Cancer discovery · 2025Article
- CARM1-Mediated MAP2K4 Methylation Potentiates the Oncogenic Functions of MAP2K4 and Constitutes a Targetable Dependency in Triple-Negative Breast Cancer.Cancer research · 2025Article
- Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance?International journal of molecular sciences · 2025Review
- Multiomics Identifies Potential Molecular Profiles Associated With Outcomes After BRAF-Targeted Therapy in Patients With BRAF V600E-Mutated Advanced Solid Tumors.JCO precision oncology · 2025Article
- The NIMA-related kinase family and cancer.Frontiers in oncology · 2025Review
- Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models.Cancer research communications · 2024Article
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Proteomic Analysis Revealed the Potential Role of MAGE-D2 in the Therapeutic Targeting of Triple-Negative Breast Cancer.Molecular & cellular proteomics : MCP · 2024Article
- Omics-Based Investigations of Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson's disease.Communications medicine · 2023Article
- Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity.Molecular cell · 2023Article
- Proteins in Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin.Molecular & cellular proteomics : MCP · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Proteomic characterization of post-translational modifications in drug discovery.Acta pharmacologica Sinica · 2022Review
- Upregulation of Receptor Tyrosine Kinase Activity and Stemness as Resistance Mechanisms to Akt Inhibitors in Breast Cancer.Cancers · 2022Article
- At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.Nature reviews. Clinical oncology · 2022Review
- Immunomodulatory Properties of PI3K/AKT/mTOR and MAPK/MEK/ERK Inhibition Augment Response to Immune Checkpoint Blockade in Melanoma and Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Cancer proteogenomics: current impact and future prospects.Nature reviews. Cancer · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 6 institutions in 2 countries.
Filip MundtThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Sandeep RajputDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Shunqiang LiDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Kelly V RugglesDepartment of Medicine, New York University Langone Health, New York, New York.
Arshag D MooradianDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Philipp MertinsThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Michael A GilletteThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Karsten KrugThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Zhanfang GuoDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Jeremy HoogDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Petra Erdmann-GilmoreDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Tina PrimeauDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Shixia HuangDan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
Dean P EdwardsDan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
Xiaowei WangDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
Xuya WangInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, New York.
Emily KawalerInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, New York.
D R ManiThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Karl R ClauserThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Feng GaoDivision of Public Health Science, Siteman Cancer Center Biostatistics Core, Washington University School of Medicine, St. Louis, Missouri.
Jingqin LuoDivision of Public Health Science, Siteman Cancer Center Biostatistics Core, Washington University School of Medicine, St. Louis, Missouri.
Sherri R DaviesDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Gary L JohnsonDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Kuan-Lin HuangDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Christopher J YoonDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Li DingDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
David FenyöInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, New York.
Matthew J EllisLester and Sue Smith Breast Center, Dan L. Duncan Comprehensive Cancer Center and Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
R Reid TownsendDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Jason M HeldDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Steven A CarrThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts. scarr@broad.mit.edu cynthiaxma@wustl.edu.
Cynthia X MaDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri. scarr@broad.mit.edu cynthiaxma@wustl.edu.
Washington University in St. Louis · USBroad Institute · USBaylor College of Medicine · USJames S. McDonnell Foundation · USNYU Langone Health · USUniversity of North Carolina at Chapel Hill · US
Funding
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MProject-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MTissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KATHERINE A. HOADLEY · 1992 to 2026
$59.3MProteo-genomic Discovery, Prioritization and Verification of Cancer BiomarkersU24CA160034 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, PAULOVICH, AMANDA G · 2011 to 2016
$16.2MIlluminating Function of the Understudied Druggable KinomeU24DK116204 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2017 to 2022
$13.6MCancer Proteome Center at Washington Univ, Univ of North Carolina & Boise StateU24CA160035 · NCI · WASHINGTON UNIVERSITY · PI CHEN, XIAN, ELLIS, MATTHEW J · 2011 to 2016
$11.8MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MCenter of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4MProteogenomic Data Analysis for Cancer Systems Biology and Clinical TranslationU24CA210972 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DING, LI, FENYO, DAVID · 2016 to 2020
$3.3MNCATS NIH HHS UL1 TR001445NCI NIH HHS P30 CA091842NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA058223NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA160034NCI NIH HHS U24 CA160035NCI NIH HHS U24 CA210972NCI NIH HHS U24 CA210986NIDDK NIH HHS U24 DK116204
Abstract
Activation of PI3K signaling is frequently observed in triple-negative breast cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel of patient-derived xenograft models of TNBC with varying responsiveness to buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts, resistance was associated with incomplete inhibition of PI3K signaling and upregulated MAPK/MEK signaling in response to buparlisib. Outlier phosphoproteome and kinome analyses identified novel candidates functionally important to buparlisib resistance, including NEK9 and MAP2K4. Knockdown of NEK9 or MAP2K4 reduced both baseline and feedback MAPK/MEK signaling and showed synthetic lethality with buparlisib
Indexed as
AminopyridinesAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMAP Kinase Kinase 4Mass SpectrometryMiceMorpholinesNIMA-Related KinasesProteomicsRNA InterferenceRNA, Small InterferingSignal TransductionAminopyridinesAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesMAP2K4 protein, humanMAP Kinase Kinase 4MorpholinesNEK9 protein, humanNIMA-Related KinasesNVP-BKM120PIK3CA protein, humanRNA, Small Interfering
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.