ArticlePLoS pathogens2012
Hsp90 inhibitors are efficacious against Kaposi Sarcoma by enhancing the degradation of the essential viral gene LANA, of the viral co-receptor EphA2 as well as other client proteins.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.PLoS pathogens · 2013Trial
- Inhibiting HSP27 activates the XBP1s/CerS1 interplay, which triggers DRP1-driven mitophagy, thereby protecting against cell death and promoting the KSHV lytic cycle in primary effusion lymphoma cells.Cell death discovery · 2026Article
- Recent Advances in Development of Kaposi's Sarcoma-Associated Herpesvirus-Latency-Associated Nuclear Antigen Targeted Therapies.Journal of medical virology · 2025Review
- Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus.Cell insight · 2024Review
- Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication.The Journal of general virology · 2024Article
- Hsp90 β is critical for the infection of severe fever with thrombocytopenia syndrome virus.Virologica Sinica · 2024Article
- EPHA2 Receptor as a Possible Therapeutic Target in Viral Infections.Current medicinal chemistry · 2024Review
- Discovery of potent heat shock protein 90 (Hsp90) inhibitors: structure-based virtual screening, molecular dynamics simulation, and biological evaluation.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Human Gammaherpesvirus 8 Oncogenes Associated with Kaposi's Sarcoma.International journal of molecular sciences · 2022Review
- Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells.iScience · 2021Article
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- Hsp90 Is Required for Snakehead Vesiculovirus Replication via Stabilization of the Viral L Protein.Journal of virology · 2021Article
- Parallel G-quadruplexes recruit the HSV-1 transcription factor ICP4 to promote viral transcription in herpes virus-infected human cells.Communications biology · 2021Article
- HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias.Blood cancer journal · 2021Article
- Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy.Frontiers in bioengineering and biotechnology · 2021Review
- Identification of Mubritinib (TAK 165) as an inhibitor of KSHV driven primary effusion lymphoma via disruption of mitochondrial OXPHOS metabolism.Oncotarget · 2020Article
- Kaposi sarcoma.Nature reviews. Disease primers · 2019Review
- Heat-shock protein 90α is involved in maintaining the stability of VP16 and VP16-mediated transactivation of α genes from herpes simplex virus-1.Molecular medicine (Cambridge, Mass.) · 2018Article
- The Hsp70 inhibitor 2-phenylethynesulfonamide inhibits replication and carcinogenicity of Epstein-Barr virus by inhibiting the molecular chaperone function of Hsp70.Cell death & disease · 2018Article
- ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus-Infected Cell Autophagic Death and Represses Tumor Growth.Molecular cancer therapeutics · 2017Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Heat-shock protein 90 (Hsp90) inhibitors exhibit activity against human cancers. We evaluated a series of new, oral bioavailable, chemically diverse Hsp90 inhibitors (PU-H71, AUY922, BIIB021, NVP-BEP800) against Kaposi sarcoma (KS). All Hsp90 inhibitors exhibited nanomolar EC(50) in culture and AUY922 reduced tumor burden in a xenograft model of KS. KS is associated with KS-associated herpesvirus (KSHV). We identified the viral latency associated nuclear antigen (LANA) as a novel client protein of Hsp90 and demonstrate that the Hsp90 inhibitors diminish the level of LANA through proteasomal degradation. These Hsp90 inhibitors also downregulated EphA2 and ephrin-B2 protein levels. LANA is essential for viral maintenance and EphA2 has recently been shown to facilitate KSHV infection; which in turn feeds latent persistence. Further, both molecules are required for KS tumor formation and both were downregulated in response to Hsp90 inhibitors. This provides a rationale for clinical testing of Hsp90 inhibitors in KSHV-associated cancers and in the eradication of latent KSHV reservoirs.
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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.