ArticleCancer research2013
The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor crizotinib in both crizotinib-sensitive and -resistant MET-driven tumor models.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 65 citations in OpenAlex.
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Combination Strategies with HSP90 Inhibitors in Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Activity-based protein profiling and global proteome analysis reveal MASTL as a potential therapeutic target in gastric cancer.Cell communication and signaling : CCS · 2024Article
- AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers.Cancer cell international · 2024Article
- Evaluation of the Anti-Metastatic Effect of Foeniculum Vulgare on the Protein Expression of HSP 70 & 90 in Balb/c Mice with 4t1 Model of Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Review
- Inhibition of HSP 90 is associated with potent anti-tumor activity in Papillary Renal Cell Carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Different HSP90 Inhibitors Exert Divergent Effect on Myxoid Liposarcoma In Vitro and In Vivo.Biomedicines · 2022Article
- Tailoring subtractive cell biopanning to identify diffuse gastric adenocarcinoma-associated antigens via human scFv antibodies.Immunology · 2020Article
- Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion.International journal of molecular sciences · 2019Review
- Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond.International journal of molecular sciences · 2019Review
- 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
- Emerging application of genomics-guided therapeutics in personalized lung cancer treatment.Annals of translational medicine · 2018Review
- A Futile Battle? Protein Quality Control and the Stress of Aging.Developmental cell · 2018Review
- The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study.Cell chemical biology · 2018Article
- Hsp90 Inhibition Reduces TLR5 Surface Expression and NF-BioMed research international · 2018Article
- Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.American journal of translational research · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The proto-oncogene MET is aberrantly activated via overexpression or mutation in numerous cancers, making it a prime anticancer molecular target. However, the clinical success of MET-directed tyrosine kinase inhibitors (TKI) has been limited due, in part, to mutations in the MET kinase domain that confer therapeutic resistance. Circumventing this problem remains a key challenge to improving durable responses in patients receiving MET-targeted therapy. MET is an HSP90-dependent kinase, and in this report we show that HSP90 preferentially interacts with and stabilizes activated MET, regardless of whether the activation is ligand-dependent or is a consequence of kinase domain mutation. In contrast, many MET-TKI show a preference for the inactive form of the kinase, and activating mutations in MET can confer resistance. Combining the HSP90 inhibitor ganetespib with the MET-TKI crizotinib achieves synergistic inhibition of MET, its downstream signaling pathways, and tumor growth in both TKI-sensitive and -resistant MET-driven tumor models. These data suggest that inclusion of an HSP90 inhibitor can partially restore TKI sensitivity to previously resistant MET mutants, and they provide the foundation for clinical evaluation of this therapeutic combination in patients with MET-driven cancers.
Indexed as
Identifiers
What OpenQuestion holds
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.