ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 166 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 phase II trial of ganetespib, a heat shock protein 90 Hsp90) inhibitor, in patients with docetaxel-pretreated metastatic castrate-resistant prostate cancer (CRPC)-a prostate cancer clinical trials consortium (PCCTC) study.Investigational new drugs · 2016Trial
- 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
- ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer.Communications chemistry · 2026Article
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Targeted drug conjugates and molecular mechanisms in overcoming lung cancer drug resistance.Discover oncology · 2025Review
- Synergistic Inhibition of PI3K and HSP90 Enhanced Antitumorigenic Efficacy in Adrenocortical Carcinoma.Research square · 2025Article
- Chaperone directed heterobifunctional molecules circumvent KRASCancer letters · 2025Article
- Predicting tumor dynamics in treated patients from patient-derived-xenograft mouse models: a translational model-based approach.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Predicting tumor dynamics in treated patients from patient-derived-xenograft mouse models: a translational model-based approach.Journal of pharmacokinetics and pharmacodynamics · 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
- Hiding in plain sight: Optimizing topoisomerase IIα inhibitors into Hsp90β selective binders.European journal of medicinal chemistry · 2024Article
- One-Pot Time-Induced Proteome Integral Solubility Alteration Assay for Automated and Sensitive Drug-Target Identification.Analytical chemistry · 2024Article
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer.Acta biochimica et biophysica Sinica · 2024Article
- DDCM: A Computational Strategy for Drug Repositioning Based on Support-Vector Regression Algorithm.International journal of molecular sciences · 2024Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Design, synthesis, and biological activity of dual monoamine oxidase A and heat shock protein 90 inhibitors, N-Methylpropargylamine-conjugated 4-isopropylresorcinol for glioblastoma.European journal of medicinal chemistry · 2023Article
- The effects of STA-9090 (Ganetespib) and venetoclax (ABT-199) combination on apoptotic pathways in human cervical cancer cells.Medical oncology (Northwood, London, England) · 2023Article
- Dose-escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF-mutant solid tumors.Cancer · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
purposeWe describe the anticancer activity of ganetespib, a novel non-geldanamycin heat shock protein 90 (HSP90) inhibitor, in non-small cell lung cancer (NSCLC) models. EXPERIMENTAL
designThe activity of ganetespib was compared with that of the geldanamycin 17-AAG in biochemical assays, cell lines, and xenografts, and evaluated in an ERBB2 YVMA-driven mouse lung adenocarcinoma model.
resultsGanetespib blocked the ability of HSP90 to bind to biotinylated geldanamycin and disrupted the association of HSP90 with its cochaperone, p23, more potently than 17-AAG. In genomically defined NSCLC cell lines, ganetespib caused depletion of receptor tyrosine kinases, extinguishing of downstream signaling, inhibition of proliferation and induction of apoptosis with IC(50) values ranging 2 to 30 nmol/L, substantially lower than those required for 17-AAG (20-3,500 nmol/L). Ganetespib was also approximately 20-fold more potent in isogenic Ba/F3 pro-B cells rendered IL-3 independent by expression of EGFR and ERBB2 mutants. In mice bearing NCI-H1975 (EGFR L858R/T790M) xenografts, ganetespib was rapidly eliminated from plasma and normal tissues but was maintained in tumor with t(1/2) 58.3 hours, supporting once-weekly dosing experiments, in which ganetespib produced greater tumor growth inhibition than 17-AAG. However, after a single dose, reexpression of mutant EGFR occurred by 72 hours, correlating with reversal of antiproliferative and proapoptotic effects. Consecutive day dosing resulted in xenograft regressions, accompanied by more sustained pharmacodynamic effects. Ganetespib also showed activity against mouse lung adenocarcinomas driven by oncogenic ERBB2 YVMA.
conclusionsGanetespib has greater potency than 17-AAG and potential efficacy against several NSCLC subsets, including those harboring EGFR or ERBB2 mutation.
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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.