ArticleInvestigational new drugs2012
Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.
Article in Investigational new drugs, 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.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Elevated plasma HSP90α as a prognostic marker in EGFR-mutant non-small cell lung cancer.Oncology letters · 2025Article
- Combination Strategies with HSP90 Inhibitors in Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Efficacy and safety of oral Chinese medicine combined with chemotherapy: a systematic review and network meta-analysis.Frontiers in pharmacology · 2025Review
- 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
- Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2023Review
- Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation.Frontiers in pharmacology · 2022Article
- Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro.Scientific reports · 2021Article
- Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma.International journal of molecular sciences · 2021Article
- Synergistic activity of Hsp90 inhibitors and anticancer agents in pancreatic cancer cell cultures.Scientific reports · 2019Article
- Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines.Translational lung cancer research · 2019Article
- Part I of GANNET53: A European Multicenter Phase I/II Trial of the Hsp90 Inhibitor Ganetespib Combined With Weekly Paclitaxel in Women With High-Grade, Platinum-Resistant Epithelial Ovarian Cancer-A Study of the GANNET53 Consortium.Frontiers in oncology · 2019Article
- Nanomedicine-Assisted Combination Therapy of NSCLC: New Platinum-Based Anticancer Drug Synergizes the Therapeutic Efficacy of Ganetespib.Nanotheranostics · 2019Article
- Ganetespib targets multiple levels of the receptor tyrosine kinase signaling cascade and preferentially inhibits ErbB2-overexpressing breast cancer cells.Scientific reports · 2018Article
- Review
- Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach.International journal of molecular sciences · 2017Review
- Reactivation of the p90RSK-CDC25C Pathway Leads to Bypass of the Ganetespib-Induced GMolecular cancer therapeutics · 2017Article
- Ganetespib overcomes resistance to PARP inhibitors in breast cancer by targeting core proteins in the DNA repair machinery.Investigational new drugs · 2017Article
- Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells.Oncology letters · 2017Article
- Hsp90 Inhibitor Ganetespib Sensitizes Non-Small Cell Lung Cancer to Radiation but Has Variable Effects with Chemoradiation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic chemotherapy using two-drug platinum-based regimens for the treatment of advanced stage non-small cell lung cancer (NSCLC) has largely reached a plateau of effectiveness. Accordingly, efforts to improve survival and quality of life outcomes have more recently focused on the use of molecularly targeted agents, either alone or in combination with standard of care therapies such as taxanes. The molecular chaperone heat shock protein 90 (Hsp90) represents an attractive candidate for therapeutic intervention, as its inhibition results in the simultaneous blockade of multiple oncogenic signaling cascades. Ganetespib is a non-ansamycin inhibitor of Hsp90 currently under clinical evaluation in a number of human malignancies, including NSCLC. Here we show that ganetespib potentiates the cytotoxic activity of the taxanes paclitaxel and docetaxel in NSCLC models. The combination of ganetespib with paclitaxel, docetaxel or another microtubule-targeted agent vincristine resulted in synergistic antiproliferative effects in the H1975 cell line in vitro. These benefits translated to improved efficacy in H1975 xenografts in vivo, with significantly enhanced tumor growth inhibition observed in combination with paclitaxel and tumor regressions seen with docetaxel. Notably, concurrent exposure to ganetespib and docetaxel improved antitumor activity in 5 of 6 NSCLC xenograft models examined. Our data suggest that the improved therapeutic indices are likely to be mechanistically multifactorial, including loss of pro-survival signaling and direct cell cycle effects resulting from Hsp90 modulation by ganetespib. Taken together, these findings provide preclinical evidence for the use of this combination to treat patients with advanced NSCLC.
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