ArticleJCO precision oncology2020
Measuring Tumor Epichaperome Expression Using [
Article in JCO precision oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting protein protein interactions and their modulators to enable new therapeutic strategies for human diseases.NPJ systems biology and applications · 2026Review
- PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease.Trends in biochemical sciences · 2025Review
- In vivo imaging of heat shock protein 90: Diagnostic tool and support for Hsp90-targeted therapy.Cell stress & chaperones · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- The role of the FKBP51-Hsp90 complex in Alzheimer's disease: An emerging new drug target.Cell stress & chaperones · 2024Review
- Epichaperome Inhibition by PU-H71-Mediated Targeting of HSP90 Sensitizes Glioblastoma Cells to Alkylator-Induced DNA Damage.Cancers · 2024Article
- Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders.Biomedicines · 2024Article
- PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.Frontiers in pharmacology · 2024Review
- Enniatin A inhibits the chaperone Hsp90 and unleashes the immune system against triple-negative breast cancer.iScience · 2023Article
- 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
- Targeting stressor-induced dysfunctions in protein-protein interaction networks via epichaperomes.Trends in pharmacological sciences · 2023Review
- The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90.International journal of molecular sciences · 2022Review
- Synthesis ofSTAR protocols · 2022Article
- Disease-specific interactome alterations via epichaperomics: the case for Alzheimer's disease.The FEBS journal · 2022Review
- The penalty of stress - Epichaperomes negatively reshaping the brain in neurodegenerative disorders.Journal of neurochemistry · 2021Review
- Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.Communications biology · 2021Article
- Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas.Cancer research · 2021Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
purposeEpichaperome network maintenance is vital to survival of tumors that express it. PU-H71 is an epichaperome inhibitor that binds to the ATP-binding site of HSP90 and has demonstrated antitumor activity in breast cancer xenograft models and clinical safety in patients. PU-positron emission tomography (PET) is a theragnostic imaging tool that allows visualization of the epichaperome target. In this phase Ib trial, we present safety and tolerability for PU-H71 plus nab-paclitaxel in HER2-negative patients with metastatic breast cancer (MBC) and the utility of PU-PET as a noninvasive predictive biomarker.
methodsWe performed a 3 + 3 dose-escalation study with escalating PU-H71 doses and standard nab-paclitaxel. The primary objective was to establish safety and determine maximum tolerated dose (MTD)/recommended phase 2 dose. Secondary objectives were to assess pharmacokinetics and clinical efficacy. Patients could enroll in a companion PU-PET protocol to measure epichaperome expression before treatment initiation to allow exploratory correlation with treatment benefit.
resultsOf the 12 patients enrolled, dose-limiting toxicity occurred in one patient (G3 neutropenic fever) at dose level 1; MTD of PU-H71 was 300 mg/m
conclusionThe combination of PU-H71 and nab-paclitaxel was well tolerated, with evidence of clinical activity. More durable disease control without progression was observed in patients with high baseline epichaperome expression. A phase II trial of this combination with PU-PET as a companion diagnostic for patient selection is currently planned.
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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.