ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Network analysis identifies an HSP90-central hub susceptible in ovarian cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Alignment of spatial transcriptomics slices across diseases, platforms and conditions.Genome medicine · 2026Article
- Functional and therapeutic significant of heat-shock protein 90 (HSP90) in reproductive cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Targeting HSP90 in Gynecologic Cancer: Molecular Mechanisms and Therapeutic Approaches.Cell biochemistry and biophysics · 2025Review
- A statistical mechanics investigation of unfolded protein response across organisms.Scientific reports · 2024Article
- HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer.Molecular oncology · 2021Article
- Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors.International journal of molecular sciences · 2020Article
- Insight updating of the molecular hallmarks in ovarian carcinoma.EJC supplements : EJC : official journal of EORTC, European Organization for Research and Treatment of Cancer ... [et al.] · 2020Article
- Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities.Cancers · 2019Review
- Roles of MYC-targeting long non-coding RNA MINCR in cell cycle regulation and apoptosis in non-small cell lung Cancer.Respiratory research · 2019Article
- Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma.PLoS computational biology · 2019Article
- RIPK1 suppresses apoptosis mediated by TNF and caspase-3 in intervertebral discs.Journal of translational medicine · 2019Article
- Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage.Journal of ovarian research · 2019Article
- Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition.Cancer biology & therapy · 2019Article
- RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance.PloS one · 2019Article
- NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice.Oncogene · 2018Article
- Ganetespib targets multiple levels of the receptor tyrosine kinase signaling cascade and preferentially inhibits ErbB2-overexpressing breast cancer cells.Scientific reports · 2018Article
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- Pre-clinical evaluation of a themosensitive gel containing epothilone B and mTOR/Hsp90 targeted agents in an ovarian tumor model.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
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- Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells.Cell death and differentiation · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeEpithelial ovarian cancer (EOC) is usually detected at an advanced stage and is frequently lethal. Although many patients respond to initial surgery and standard chemotherapy consisting of a platinum-based agent and a taxane, most experience recurrence and eventually treatment-resistant disease. Although there have been numerous efforts to apply protein-targeted agents in EOC, these studies have so far documented little efficacy. Our goal was to identify broadly susceptible signaling proteins or pathways in EOC. EXPERIMENTAL
designAs a new approach, we conducted data-mining meta-analyses integrating results from multiple siRNA screens to identify gene targets that showed significant inhibition of cell growth. On the basis of this meta-analysis, we established that many genes with such activity were clients of the protein chaperone HSP90. We therefore assessed ganetespib, a clinically promising second-generation small-molecule HSP90 inhibitor, for activity against EOC, both as a single agent and in combination with cytotoxic and targeted therapeutic agents.
resultsGanetespib significantly reduced cell growth, induced cell-cycle arrest and apoptosis in vitro, inhibited growth of orthotopic xenografts and spontaneous ovarian tumors in transgenic mice in vivo, and inhibited expression and activation of numerous proteins linked to EOC progression. Importantly, paclitaxel significantly potentiated ganetespib activity in cultured cells and tumors. Moreover, combined treatment of cells with ganetespib and siRNAs or small molecules inhibiting genes identified in the meta-analysis in several cases resulted in enhanced activity.
conclusionThese results strongly support investigation of ganetespib, a single-targeted agent with effects on numerous proteins and pathways, in augmenting standard EOC therapies.
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