ArticleBritish journal of haematology2009
The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas.
Article in British journal of haematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01168752 (Phase I Dose-escalation, Pharmacokinetic and Pharmacodynamic Study of Debio 0932, a Novel Hsp90-inhibitor, Administered Orally, in Patients With Advanced Solid Tumours or Lymphoma), which is not on this map. Cited by 16 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.
Phase I Dose-escalation, Pharmacokinetic and Pharmacodynamic Study of Debio 0932, a Novel Hsp90-inhibitor, Administered Orally, in Patients With Advanced Solid Tumours or Lymphoma
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer.Breast cancer research and treatment · 2013Trial
- SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.Cell death & disease · 2023Article
- BRAF inhibition curtails IFN-gamma-inducible PD-L1 expression and upregulates the immunoregulatory protein galectin-1 in melanoma cells.Molecular oncology · 2020Article
- Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage.Biomolecules & therapeutics · 2019Article
- Article
- Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline.Oncotarget · 2015Article
- Heat shock protein 90 and role of its chemical inhibitors in treatment of hematologic malignancies.Pharmaceuticals (Basel, Switzerland) · 2012Article
- Article
- HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition.The Journal of experimental medicine · 2012Article
- Therapy of newly diagnosed follicular lymphoma.Frontiers in oncology · 2012Article
- Hsp90 (heat shock protein 90) inhibitor occupancy is a direct determinant of client protein degradation and tumor growth arrest in vivo.The Journal of biological chemistry · 2010Article
- BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy.The Journal of clinical investigation · 2010Article
- Virtual prototyping study shows increased ATPase activity of Hsp90 to be the key determinant of cancer phenotype.Systems and synthetic biology · 2010Article
- Hsp90 as a gatekeeper of tumor angiogenesis: clinical promise and potential pitfalls.Journal of oncology · 2010Article
- A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas.Nature medicine · 2009Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein 90 (HSP90) is a molecular chaperone that stabilizes critical client proteins in multiple cancers. Gene expression profiling was utilized to characterize HSP90 isoform expression in primary human diffuse large B-cell lymphomas (DLBCLs). HSP90 alpha and beta isoforms were differentially expressed in subsets of tumours defined by their transcriptional profiles. Thereafter, we assessed the activity of the HSP90 inhibitor, IPI-504, in an extensive panel of DLBCL cell lines. IPI-504, which interacts with the conserved ATP-binding site in both HSP90 isoforms, inhibited proliferation and induced apoptosis in the majority of DLBCL cell lines at low micromolar concentrations. IPI-504-sensitive cell lines expressed high levels of the HSP90 client protein, pAKT, and exhibited dose-dependent decreases in pAKT levels following IPI-504 treatment and significantly reduced proliferation following AKT RNAi. Furthermore, the combination of low-dose (<1 micromol/l) IPI-504 and the AKT/Pi3K pathway inhibitor, LY24009, was synergistic in IPI-504-sensitive DLBCL cell lines. Low-dose IPI-504 was also synergistic with the chemotherapeutic agent, doxorubicin. The HSP90 inhibitor IPI-504 warrants further investigation in DLBCL alone and in combination with identified client protein inhibitors and active chemotherapeutic agents.
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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.