ArticleCommunications biology2021
Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.
Open access · goldAbstract read
In one paragraph
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 17% 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
18 citing papers in PubMed, 24 citations in OpenAlex.
- Embracing diversity: Post-translational modifications, the chaperone code, and the emergence of new chaperone entities.Cell stress & chaperones · 2026Review
- Mapping Dysfunctional Protein-Protein Interactions in Disease.Journal of visualized experiments : JoVE · 2025Article
- PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease.Trends in biochemical sciences · 2025Review
- Systems-Level Interactome Mapping Reveals Actionable Protein Network Dysregulation Across the Alzheimer's Disease Spectrum.Research square · 2025Article
- Review
- Introducing dysfunctional Protein-Protein Interactome (dfPPI) - A platform for systems-level protein-protein interaction (PPI) dysfunction investigation in disease.Current opinion in structural biology · 2024Review
- Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders.Biomedicines · 2024Article
- Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.Research square · 2024Article
- PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.Frontiers in pharmacology · 2024Review
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action.Biomedicines · 2023Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.Nature communications · 2023Article
- Tenth International Symposium on the Hsp90 chaperone machine : Switzerland, October 19-23, 2022.Cell stress & chaperones · 2023Review
- Integrating Protein Interaction Surface Prediction with a Fragment-Based Drug Design: Automatic Design of New Leads with Fragments on Energy Surfaces.Journal of chemical information and modeling · 2023Article
- Targeting stressor-induced dysfunctions in protein-protein interaction networks via epichaperomes.Trends in pharmacological sciences · 2023Review
- Use of Native-PAGE for the Identification of Epichaperomes in Cell Lines.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.Communications biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
40 authors at 6 institutions in 2 countries.
Suhasini Joshi *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Erica DaGama Gomes *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Tai Wang *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Adriana CorbenDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Tony TaldoneChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Srinivasa GanduChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-8288-1523
Chao XuChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Sahil SharmaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7281-9224
Salma BuddasethChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Pengrong YanChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0021-6461
Lon Yin L ChanChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Askan GokceDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Vinagolu K RajasekharDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Lisa ShresthaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Palak PanchalChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Justina AlmodovarChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Chander S DigwalChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-8784-1096
Anna RodinaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-3894-6438
Swathi MeruguChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
NagaVaraKishore PillarsettyDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-1750-7436
Vlad MicleaFaculty of Automation and Computer Science, Technical University of Cluj-Napoca, Cluj-Napoca, CJ, 400114, Romania.ORCID http://orcid.org/0000-0002-5781-5433
Radu I PeterFaculty of Automation and Computer Science, Technical University of Cluj-Napoca, Cluj-Napoca, CJ, 400114, Romania.ORCID http://orcid.org/0000-0003-0114-966X
Wanyan WangChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0332-2702
Stephen D GinsbergCenter for Dementia Research, Nathan Kline Institute, Orangeburg, NY, 10962, USA.
Laura TangDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Marissa MattarAntitumour Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Elisa de StanchinaAntitumour Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Kenneth H YuDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Maeve LoweryDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Olivera Grbovic-HuezoDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-8011-7801
Eileen M O'ReillyDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-8076-9199
Yelena JanjigianDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, 10065, USA.
John H HealeyDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-0802-1186
William R JarnaginDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Peter J AllenDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Chris SanderDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Hediye Erdjument-BromageDepartment of Cell Biology, New York University Grossman School of Medicine, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0003-0224-3594
Thomas A NeubertDepartment of Cell Biology, New York University Grossman School of Medicine, New York, NY, 10016, USA.
Steven D LeachDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-2689-1871
Gabriela ChiosisChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chiosisg@mskcc.org.ORCID http://orcid.org/0000-0003-0486-6920
Memorial Sloan Kettering Cancer Center · USNew York University · USTechnical University of Cluj-Napoca · RODartmouth College · USHarvard University · USNathan Kline Institute for Psychiatric Research · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MTranslating Stress Response Targeted Therapy for B-Cell LymphomasP50CA192937 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DALLA-FAVERA, RICCARDO, ZELENETZ, ANDREW D. · 2016 to 2020
$10.9MMSKCC Pilot Center for Precision Disease ModelingU54OD020355 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI LOWE, SCOTT W., SOLIT, DAVID B. · 2015 to 2019
$9.9MProject 3: Structural Basis for grp94 Drug Development and Chaperone FunctionP01CA186866 · NCI · OHIO STATE UNIVERSITY · PI LI, ZIHAI · 2015 to 2019
$6.7MImpact of sex differences on the trajectory of interactome dysfunctions across the AD spectrumR01AG074004 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2025
$6.0MChaperome networks in Alzheimer's diseaseR01AG067598 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI ARANCIO, OTTAVIO, CHIOSIS, GABRIELA · 2021 to 2025
$5.9MNeuropathology and inflammation in a nonhuman primate model of insulin resistance/metabolic syndromeR01AG085572 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STEPHEN D GINSBERG, PETER J HAVEL · 2024 to 2026
$3.8MBiomarkers for predicting response to Hsp90 therapyR01CA172546 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, DUNPHY, MARK P. · 2013 to 2017
$2.9MTargeting the heat shock response for the therapy of DLBCLR01CA155226 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHIOSIS, GABRIELA, MELNICK, ARI M. · 2011 to 2015
$2.5MA chemical chaperomics platform for ADR56AG061869 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA · 2018 to 2019
$1.8MSelective interactome vulnerability across the Alzheimer’s disease spectrumR56AG072599 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2021
$1.2MLTQ-Orbitrap Mass Spectrometer.S10RR027990 · NCRR · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NEUBERT, THOMAS A · 2011 to 2011
$600kNCI NIH HHS P01 CA186866NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA192937NCI NIH HHS R01 CA155226NCI NIH HHS R01 CA172546NCRR NIH HHS S10 RR027990NIA NIH HHS R01 AG067598NIA NIH HHS R01 AG074004NIA NIH HHS R01 AG085572NIA NIH HHS R21 AG028811NIA NIH HHS R56 AG061869NIA NIH HHS R56 AG072599NIH HHS U54 OD020355
Abstract
Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore primes interactomes to enhance vulnerability and improve treatment efficacy, enabling therapeutics with traditionally poor performance to become highly efficacious. These findings provide proof-of-principle for a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks.
Indexed as
Epigenesis, GeneticGenomeProtein Interaction MappingProtein Interaction MapsAnimalsFemaleHeterograftsHumansMiceMolecular ChaperonesNeoplasmsSignal TransductionMolecular Chaperones
Identifiers
What Socratic holds
Textmetadata
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 Socratic graph.