ArticleThe Journal of clinical investigation2015
Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 42 citations in OpenAlex.
- A network toxicology and molecular docking study predicting putative molecular targets and pathways linking bisphenol a exposure to diffuse large B-cell lymphoma.Discover oncology · 2026Article
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.Cell death & disease · 2023Article
- Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- The penalty of stress - Epichaperomes negatively reshaping the brain in neurodegenerative disorders.Journal of neurochemistry · 2021Review
- Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas.Cancer research · 2021Article
- Heat Shock Proteins in Lymphoma Immunotherapy.Frontiers in immunology · 2021Review
- First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- A Chemical Biology Approach to the Chaperome in Cancer-HSP90 and Beyond.Cold Spring Harbor perspectives in biology · 2020Review
- HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Chaperome Networks - Redundancy and Implications for Cancer Treatment.Advances in experimental medicine and biology · 2020Review
- Germinal center-derived lymphomas: The darkest side of humoral immunity.Immunological reviews · 2019Review
- Chaperome heterogeneity and its implications for cancer study and treatment.The Journal of biological chemistry · 2019Review
- Adapting to stress - chaperome networks in cancer.Nature reviews. Cancer · 2018Review
- How Biophysical Forces Regulate Human B Cell Lymphomas.Cell reports · 2018Article
- Role of Bruton's tyrosine kinase in B cells and malignancies.Molecular cancer · 2018Review
- Drug-perturbation-based stratification of blood cancer.The Journal of clinical investigation · 2018Article
- Proteomic interrogation of HSP90 and insights for medical research.Expert review of proteomics · 2017Review
- Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma.Molecular cancer therapeutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Rationally designed combinations of targeted therapies for refractory cancers, such as activated B cell-like diffuse large B cell lymphoma (ABC DLBCL), are likely required to achieve potent, durable responses. Here, we used a pharmacoproteomics approach to map the interactome of a tumor-enriched isoform of HSP90 (teHSP90). Specifically, we chemically precipitated teHSP90-client complexes from DLBCL cell lines with the small molecule PU-H71 and found that components of the proximal B cell receptor (BCR) signalosome were enriched within teHSP90 complexes. Functional assays revealed that teHSP90 facilitates BCR signaling dynamics by enabling phosphorylation of key BCR signalosome components, including the kinases SYK and BTK. Consequently, treatment of BCR-dependent ABC DLBCL cells with PU-H71 attenuated BCR signaling, calcium flux, and NF-κB signaling, ultimately leading to growth arrest. Combined exposure of ABC DLBCL cell lines to PU-H71 and ibrutinib, a BCR pathway inhibitor, more potently suppressed BCR signaling than either drug alone. Correspondingly, PU-H71 combined with ibrutinib induced synergistic killing of lymphoma cell lines, primary human lymphoma specimens ex vivo, and lymphoma xenografts in vivo, without notable toxicity. Together, our results demonstrate that a pharmacoproteome-driven rational combination therapy has potential to provide more potent BCR-directed therapy for ABC DLCBL patients.
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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.