ArticleCancer discovery2015
Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST tumor growth.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 118 citations in OpenAlex.
- ctDNA as a Molecular Biomarker in the Phase II Trial of Imatinib plus Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- IGF2-associated tumor cells and APOE-positive macrophages define an imatinib resistance-associated niche in gastrointestinal stromal tumors.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Rare Molecular Variants of Gastrointestinal Stromal Tumors (GISTs): Clinical Implications and Overview of Current Evidence.Targeted oncology · 2026Review
- Periorbital hyperpigmentation as the initial manifestation of smoldering multiple myeloma in a patient with coexisting gastrointestinal stromal tumor: a case report and narrative literature review.Frontiers in oncology · 2026Article
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- Feasibility of Patient-Derived 3D Gastrointestinal Stromal Tumour Models as Alternatives for In Vivo Mouse Models.International journal of molecular sciences · 2025Article
- Golgi retention of KIT in gastrointestinal stromal tumour cells is phospholipase D activity-dependent.Scientific reports · 2025Article
- ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor.Cancer chemotherapy and pharmacology · 2025Article
- Aptamer-based drug delivery for targeted therapy of imatinib-resistant gastrointestinal stromal tumor.Theranostics · 2025Article
- Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update.Current treatment options in oncology · 2024Review
- Modeling human gastric cancers in immunocompetent mice.Cancer biology & medicine · 2024Review
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- Exploring Perforated Jejunal GIST: A Rare Case Report and Review of Molecular and Clinical Literature.Current issues in molecular biology · 2024Article
- Cell-permeable PI3 kinase competitive peptide inhibits KIT mutant mediated tumorigenesis of gastrointestinal stromal tumor (GIST).Molecular biology reports · 2024Article
- Molecular Advances in the Treatment of Advanced Gastrointestinal Stromal Tumor.The oncologist · 2023Review
- Efficacy of post-first-line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta-analysis.Cancer medicine · 2023Article
- Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers.Molecular cancer · 2023Review
- ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.Science advances · 2023Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledGastrointestinal stromal tumor (GIST), originating from the interstitial cells of Cajal (ICC), is characterized by frequent activating mutations of the KIT receptor tyrosine kinase. Despite the clinical success of imatinib, which targets KIT, most patients with advanced GIST develop resistance and eventually die of the disease. The ETS family transcription factor ETV1 is a master regulator of the ICC lineage. Using mouse models of Kit activation and Etv1 ablation, we demonstrate that ETV1 is required for GIST initiation and proliferation in vivo, validating it as a therapeutic target. We further uncover a positive feedback circuit where MAP kinase activation downstream of KIT stabilizes the ETV1 protein, and ETV1 positively regulates KIT expression. Combined targeting of ETV1 stability by imatinib and MEK162 resulted in increased growth suppression in vitro and complete tumor regression in vivo. The combination strategy to target ETV1 may provide an effective therapeutic strategy in GIST clinical management. SIGNIFICANCE: ETV1 is a lineage-specific oncogenic transcription factor required for the growth and survival of GIST. We describe a novel strategy of targeting ETV1 protein stability by the combination of MEK and KIT inhibitors that synergistically suppress tumor growth. This strategy has the potential to change first-line therapy in GIST clinical management.
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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.