ArticlePloS one2011
Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 78 citations in OpenAlex.
- A Phase II Study of Ganetespib as Second-line or Third-line Therapy for Metastatic Pancreatic Cancer.American journal of clinical oncology · 2018Trial
- A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor resistance in non-small cell lung cancer.Cancer discovery · 2013Trial
- Targeting heat shock protein 90 with usnic acid relieves immune suppression via aryl hydrocarbon receptor-mediated mechanisms in lung cancer.Molecular biomedicine · 2025Article
- Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1.Molecular and cellular biology · 2025Article
- Identification of Dinaciclib and Ganetespib as anti-inflammatory drugs using a novel HTP screening assay that targets IFNγ-dependent PD-L1.Frontiers in immunology · 2025Article
- Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2023Review
- Ganetespib with Methotrexate Acts Synergistically to Impede NF-κB/p65 Signaling in Human Lung Cancer A549 Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.NPJ breast cancer · 2022Article
- A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.Oncogenesis · 2021Article
- Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance.Communications biology · 2021Article
- Heat Shock Proteins and PD-1/PD-L1 as Potential Therapeutic Targets in Myeloproliferative Neoplasms.Cancers · 2020Review
- Finding a Jill for JAK: Assessing Past, Present, and Future JAK Inhibitor Combination Approaches in Myelofibrosis.Cancers · 2020Review
- HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma.OncoTargets and therapy · 2020Article
- Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage.Biomolecules & therapeutics · 2019Article
- Overview of the Mutational Landscape in Primary Myelofibrosis and Advances in Novel Therapeutics.Asian Pacific journal of cancer prevention : APJCP · 2019Review
- Anti-TGEV Miller Strain Infection Effect ofFrontiers in microbiology · 2019Article
- Consecutive Day HSP90 Inhibitor Administration Improves Efficacy in Murine Models of KIT-Driven Malignancies and Canine Mast Cell Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- IL4 and IL21 cooperate to induce the high Bcl6 protein level required for germinal center formation.Immunology and cell biology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is accumulating evidence that dysregulated JAK signaling occurs in a wide variety of cancer types. In particular, mutations in JAK2 can result in the constitutive activation of STAT transcription factors and lead to oncogenic growth. JAK kinases are established Hsp90 client proteins and here we show that the novel small molecule Hsp90 inhibitor ganetespib (formerly STA-9090) exhibits potent in vitro and in vivo activity in a range of solid and hematological tumor cells that are dependent on JAK2 activity for growth and survival. Of note, ganetespib treatment results in sustained depletion of JAK2, including the constitutively active JAK2(V617F) mutant, with subsequent loss of STAT activity and reduced STAT-target gene expression. In contrast, treatment with the pan-JAK inhibitor P6 results in only transient effects on these processes. Further differentiating these modes of intervention, RNA and protein expression studies show that ganetespib additionally modulates cell cycle regulatory proteins, while P6 does not. The concomitant impact of ganetespib on both cell growth and cell division signaling translates to potent antitumor efficacy in mouse models of xenografts and disseminated JAK/STAT-driven leukemia. Overall, our findings support Hsp90 inhibition as a novel therapeutic approach for combating diseases dependent on JAK/STAT signaling, with the multimodal action of ganetespib demonstrating advantages over JAK-specific inhibitors.
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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.