ArticleCancer cell2016
Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma.
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Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91citing papers in PubMed
17.7field-weighted citation impact, top 1% of its field
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91 citing papers in PubMed, 166 citations in OpenAlex.
- A comprehensive pharmacological survey across heterogeneous patient-derived glioblastoma stem cell models.iScience · 2026Article
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- Endogenous inhibitors of PP2A activate oncogenic and DNA damage response kinases in glioblastoma.Cancer letters · 2026Article
- Voxtalisib inhibits enterovirus 71 replication by downregulating host RAN and restoring IFN-STAT signaling.Journal of advanced research · 2026Article
- Repeat resection for recurrent glioblastoma - does timing matter?Journal of neuro-oncology · 2026Article
- Proteomics in Antitumor Drug Target Discovery, Toxicity, Resistance, and Precision Oncology.Drug design, development and therapy · 2026Review
- Single-cell profiling of kinase substrate phosphorylation by single-molecule imaging.PloS one · 2026Article
- Single-cell multi-omics in cancer immunotherapy: from tumor heterogeneity to personalized precision treatment.Molecular cancer · 2025Review
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Identification of drug-resistant individual cells within tumors by semi-supervised transfer learning from bulk to single-cell transcriptome.Communications biology · 2025Article
- Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma.Cancer letters · 2024Article
- Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk-benefit analysis.Journal of neuro-oncology · 2024Article
- Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.International journal of molecular sciences · 2024Review
- Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.Cell genomics · 2024Article
- Non-Mass Spectrometric Targeted Single-Cell Metabolomics.Trends in analytical chemistry : TRAC · 2023Article
- Mass spectrometry-based phosphoproteomics in clinical applications.Trends in analytical chemistry : TRAC · 2023Article
- Deep Learning in Phosphoproteomics: Methods and Application in Cancer Drug Discovery.Proteomes · 2023Review
- Enabling Single-Cell Drug Response Annotations from Bulk RNA-Seq Using SCAD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.Cancers · 2023Review
- Phosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells.Journal of proteome research · 2022Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 2 countries.
Wei WeiDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA; Department of Applied Physics and Materials Science, California Institute of Technology, Pasadena, CA 91125, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Young Shik ShinDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Min XueDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA.
Tomoo MatsutaniLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Kenta MasuiLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Huijun YangLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Shiro IkegamiLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Yuchao GuLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Ken HerrmannDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dazy JohnsonDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xiangming DingDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kiwook HwangDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA.
Jungwoo KimDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA.
Jian ZhouDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yapeng SuDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA.
Xinmin LiDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bruno BonettiDepartment of Neurological and Movement Sciences, University of Verona, Verona, 37134, Italy.
Rajesh ChopraCelgene Corporation, San Diego, CA 92121, USA.
C David JamesDepartment of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Webster K CaveneeLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Timothy F CloughesyDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Paul S MischelLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: pmischel@ucsd.edu.
James R HeathDivision of Chemistry and Chemical Engineering, NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA 91125, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: heath@caltech.edu.
Beatrice GiniLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
University of California, Los Angeles · USCalifornia Institute of Technology · USLudwig Cancer Research · USUniversity of California, San Diego · USNorthwestern University · USUniversity of Verona · IT
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MWomen's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5MVIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9MUCLA Institute for Molecular Medicine (IMED) CoreU54CA151819 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DAVIS, MARK E · 2010 to 2014
$12.1MRepurposing of cancer therapeutics for treatment of patients with COVID-19 diseaseU54CA199090 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI HEATH, JAMES R., RIBAS, ANTONI · 2015 to 2020
$11.4MThe role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4MCancer Research UK 11566NCI NIH HHS 5U54CA 151819NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA060553NCI NIH HHS U54 CA151819NCI NIH HHS U54 CA199090NINDS NIH HHS NS73831NINDS NIH HHS R01 NS073831
Abstract
Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.
Indexed as
Molecular Targeted TherapyAdaptation, PhysiologicalAnimalsAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsButadienesDasatinibDrug Resistance, NeoplasmDrug SynergismErbB ReceptorsGene Expression ProfilingGenes, erbB-1GlioblastomaHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2ButadienesCC214-2DasatinibEGFR protein, humanErbB ReceptorsMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Multiprotein ComplexesNeoplasm ProteinsNitrilesPhosphoproteinsProtein Kinase InhibitorsPyrazinesTOR Serine-Threonine KinasesU 0126
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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.