Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2008
Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 187 citations in OpenAlex.
- Reliability of BRAF mutation detection using plasma sample: A systematic review and meta-analysisMedicine · 2021Pooled it
- A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma.Investigational new drugs · 2012Trial
- Heat Shock Proteins as Targets for Cancer Therapeutics.Journal of clinical medicine · 2026Review
- Nanotechnological strategies to increase the oxygen content of the tumor.Frontiers in pharmacology · 2023Review
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas.Melanoma research · 2021Article
- National Institute on Aging Workshop: Repurposing Drugs or Dietary Supplements for Their Senolytic or Senomorphic Effects: Considerations for Clinical Trials.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
- First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer.Molecular biology of the cell · 2020Article
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- Inhibitors of HSP90 in melanoma.Apoptosis : an international journal on programmed cell death · 2020Review
- Two closed ATP- and ADP-dependent conformations in yeast Hsp90 chaperone detected by Mn(II) EPR spectroscopic techniques.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity.Theranostics · 2020Article
- Suppression of Esophageal Cancer Stem-like Cells by SNX-2112 Is Enhanced by STAT3 Silencing.Frontiers in pharmacology · 2020Article
- Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage.Biomolecules & therapeutics · 2019Article
- Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine.Advanced pharmaceutical bulletin · 2019Article
- Fibroblast growth factor signals regulate transforming growth factor-β-induced endothelial-to-myofibroblast transition of tumor endothelial cells via Elk1.Molecular oncology · 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
35 more citing papers are in PubMed but not listed here.
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 6 institutions in 2 countries.
Funding
Abstract
purposeActivation of the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/AKT pathway seems to be critical for melanoma proliferation. Components of these pathways are client proteins of heat-shock protein 90 (hsp90), suggesting that inhibition of hsp90 could have significant antimelanoma effects. We conducted a phase II trial using the hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in melanoma patients. The primary end points were clinical responses and whether treatment inhibited MAPK pathway activity. EXPERIMENTAL
designMelanoma patients with measurable disease were stratified on the basis of whether or not their tumor harbored a V600E BRAF mutation. The hsp90 inhibitor 17-AAG was administered i.v. once weekly x 6 weeks at 450 mg/m2. Tumor biopsies were obtained pretreatment and 18 to 50 hours after the first dose of 17-AAG, and were snap-frozen.
resultsFifteen evaluable patients were treated; nine had BRAF mutations and six were wild-type. No objective responses were observed. Western blot analysis of tumor biopsies showed an increase in hsp70 and a decrease in cyclin D1 expression in the posttreatment biopsies but no significant effect on RAF kinases or phospho-extracellular signal-regulated kinase expression. Plasma analyzed by mutant-specific PCR for V600E BRAF showed 86% sensitivity and 67% specificity in predicting tumor DNA sequencing results.
conclusionsAt this dose and schedule of 17-AAG, the effects of 17-AAG on RAF kinase expression were short-lived, and no objective antimelanoma responses were seen. Future trials in melanoma should focus on a more potent hsp90 inhibitor or a formulation that can be administered chronically for a more prolonged suppression of the MAPK pathway.
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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.