ArticleClinical cancer research : an official journal of the American Association for Cancer Research2005
Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 366 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
366 citing papers in PubMed, 2 syntheses or guidelines pooled it, 828 citations in OpenAlex.
- A systematic review and network meta-analysis of the efficacy and safety of third-line and over third-line therapy after imatinib and TKI resistance in advanced gastrointestinal stromal tumor.Frontiers in pharmacology · 2022Pooled it
- Pooled it
- 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
- Imatinib alternating with regorafenib compared to imatinib alone for the first-line treatment of advanced gastrointestinal stromal tumor: The AGITG ALT-GIST intergroup randomized phase II trial.British journal of cancer · 2025Trial
- Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial.Nature medicine · 2024Trial
- Broad spectrum of regorafenib activity on mutant KIT and absence of clonal selection in gastrointestinal stromal tumor (GIST): correlative analysis from the GRID trial.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Trial
- 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
- Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib.JAMA oncology · 2018Trial
- Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib.British journal of cancer · 2017Trial
- Trial
- Trial
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- Current Evidence for Circulating Tumor DNA in Sarcoma: Challenges and Opportunities for Clinical Application.Journal of surgical oncology · 2026Review
- Non-Coding RNAs in Gastrointestinal Stromal Tumors: Regulatory Networks, Drug Resistance, and Clinical Implications.International journal of molecular sciences · 2026Review
- Limitations of Post-treatment TNM Staging After Neoadjuvant Targeted Therapy and Surgery for Gastrointestinal Stromal Tumors: A SEER-Based Study with Two-Center External Validation.Annals of surgical oncology · 2026Article
- Metabolic profile alterations as early indicators of gastrointestinal stromal tumors (GISTs) recurrence and imatinib resistance.Journal of gastrointestinal oncology · 2026Article
- Nestin promotes imatinib resistance in gastrointestinal stromal tumors by enhancing PINK1-dependent mitophagy.Molecular medicine (Cambridge, Mass.) · 2026Article
- Design and Synthesis of BLU-654, a Potent and Selective Mutant KIT V654A Inhibitor for the Treatment of Imatinib-Resistant GIST.Journal of medicinal chemistry · 2026Article
- Gastrointestinal Stromal Tumor: History, Molecular Subtypes, and Risk Stratification.Journal of gastric cancer · 2026Review
306 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Most gastrointestinal stromal tumors (GIST) have an activating mutation in either KIT or PDGFRA. Imatinib is a selective tyrosine kinase inhibitor and achieves a partial response or stable disease in about 80% of patients with metastatic GIST. It is now clear that some patients with GIST develop resistance to imatinib during chronic therapy. To identify the mechanism of resistance, we studied 31 patients with GIST who were treated with imatinib and then underwent surgical resection. There were 13 patients who were nonresistant to imatinib, 3 with primary resistance, and 15 with acquired resistance after initial benefit from the drug. There were no secondary mutations in KIT or PDGFRA in the nonresistant or primary resistance groups. In contrast, secondary mutations were found in 7 of 15 (46%) patients with acquired resistance, each of whom had a primary mutation in KIT exon 11. Most secondary mutations were located in KIT exon 17. KIT phosphorylation was heterogeneous and did not correlate with clinical response to imatinib or mutation status. That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies.
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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.