ArticleCancer research2009
Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 88 citations in OpenAlex.
- Targeting the SETD2-FTO-KIT pathway as a pharmacological strategy for TKI-refractory GIST.Acta pharmaceutica Sinica. B · 2026Article
- Structure-based scaffold hopping reveals strategies to overcome oncogenic KIT and PDGFRA mutation-driven drug-resistance in GIST.Nature communications · 2026Article
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- Preclinical Models of Visceral Sarcomas.Biomolecules · 2023Review
- Plasma Sequencing for Patients with GIST-Limitations and Opportunities in an Academic Setting.Cancers · 2022Article
- Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability.Scientific reports · 2022Article
- Quantitative proteomic analysis of aberrant expressed lysine acetylation in gastrointestinal stromal tumors.Clinical proteomics · 2021Article
- The Use of Molecular Subtypes for Precision Therapy of Recurrent and Metastatic Gastrointestinal Stromal Tumor.OncoTargets and therapy · 2020Review
- Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and Are Targetable by BET Bromodomain Inhibition.Cancer research · 2019Article
- Mechanisms of resistance to a PI3K inhibitor in gastrointestinal stromal tumors: anCancer management and research · 2019Article
- Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth.Molecular oncology · 2018Article
- Survivin is a novel transcription regulator of KIT and is downregulated by miRNA-494 in gastrointestinal stromal tumors.International journal of cancer · 2018Article
- Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression.Journal of virology · 2018Article
- Genetic progression in gastrointestinal stromal tumors: mechanisms and molecular interventions.Oncotarget · 2017Review
- Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors.Targeted oncology · 2017Review
- Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis.Oncotarget · 2017Article
- Article
- Pharmacological treatment options for mast cell activation disease.Naunyn-Schmiedeberg's archives of pharmacology · 2016Review
- HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat.The journal of pathology. Clinical research · 2016Article
- miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours.Molecular oncology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor A (PDGFRA), and treatment with the tyrosine kinase inhibitor imatinib yields responses in the majority of patients. However, most patients develop secondary resistance, which is associated with a dismal prognosis. Histone deacetylase inhibitors (HDACI) have been shown to enhance imatinib activity in imatinib-resistant chronic myelogenous leukemia. Against this background, we explored whether HDACI might provide an alternative therapeutic strategy to KIT/PDGFRA kinase inhibitors in GIST. Inhibition of cell proliferation by HDACI was seen in KIT-positive but not in KIT-negative GIST cell lines, suggesting that HDACI activity is mainly conferred by targeting oncogenic KIT. KIT activity, expression, and activation of downstream pathways were strongly inhibited by several HDACI (SAHA, LBH589, VPA, trichostatin A, and NaButyrate). SAHA and LBH589 induced apoptosis in KIT-positive GIST, and strong synergism with imatinib was observed at low concentrations of SAHA and LBH589. Mechanistically, treatment with HDACI reduced KIT mRNA transcript levels and led to strong acetylation of HSP90, interfering with its activity as KIT chaperone. These results provide preclinical evidence for a disease-specific effect of HDACI in KIT-positive GIST, which could translate into therapeutic activity.
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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.