ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017
Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Feasibility of Patient-Derived 3D Gastrointestinal Stromal Tumour Models as Alternatives for In Vivo Mouse Models.International journal of molecular sciences · 2025Article
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications.Heliyon · 2025Article
- SHP2 inhibition and adjuvant therapy synergistically target KIT-mutant GISTs via ERK1/2-regulated GSK3β/cyclin D1 pathway.Clinical and translational medicine · 2025Article
- Case Report: Neoadjuvant therapy with ripretinib for gastrointestinal stromal tumor: a case report.Frontiers in pharmacology · 2025Article
- Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update.Current treatment options in oncology · 2024Review
- Endoscopic Characteristics of Small-Bowel Gastrointestinal Stromal Tumors Detected During Single-Balloon Enteroscopy: A Retrospective Analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- Refining Prognosis in Localized Gastrointestinal Stromal Tumor: Clinical Significance of Phosphatase and Tensin Homolog Low Expression and Gene Loss.JCO precision oncology · 2022Article
- The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours.Targeted oncology · 2022Review
- Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor.Cancers · 2021Article
- Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis.Oncogene · 2021Article
- Identification of Wee1 as a target in combination with avapritinib for gastrointestinal stromal tumor treatment.JCI insight · 2021Article
- Inhibition of AKT-Signaling Sensitizes Soft Tissue Sarcomas (STS) and Gastrointestinal Stromal Tumors (GIST) to Doxorubicin via Targeting of Homology-Mediated DNA Repair.International journal of molecular sciences · 2020Article
- Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.Molecular biology reports · 2020Review
- Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study.British journal of cancer · 2020Article
- The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression.Frontiers in immunology · 2020Review
- Farnesiferol C Induces Apoptosis in Chronic Myelogenous Leukemia Cells as an Imatinib Sensitizer via Caspase Activation and HDAC (Histone Deacetylase) Inactivation.International journal of molecular sciences · 2019Article
- The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.Cancers · 2019Review
- Development of Fangjiomics for Systems Elucidation of Synergistic Mechanism Underlying Combination Therapy.Computational and structural biotechnology journal · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGastrointestinal stromal tumors (GIST) generally harbor activating mutations in the receptor tyrosine kinase KIT or in the related platelet-derived growth factor receptor alpha (PDGFRA). GIST treated with imatinib mesylate or second-line therapies that target mutant forms of these receptors generally escape disease control and progress over time. Inhibiting additional molecular targets may provide more substantial disease control. Recent studies have implicated the PI3K/AKT pathway in the survival of imatinib mesylate-resistant GIST cell lines and tumors. EXPERIMENTAL
designHere, we performed in vitro and in vivo studies evaluating the novel combination of imatinib mesylate with the AKT inhibitor MK-2206 in GIST. Whole-transcriptome sequencing (WTS) of xenografts was performed to explore the molecular aspects of tumor response to this novel combination and to potentially identify additional therapeutic targets in GIST.
resultsThis drug combination demonstrated significant synergistic effects in a panel of imatinib mesylate-sensitive and -resistant GIST cell lines. Furthermore, combination therapy provided significantly greater efficacy, as measured by tumor response and animal survival, in imatinib mesylate-sensitive GIST xenografts as compared with treatment with imatinib mesylate or MK-2206 alone. WTS implicated two neural genes, brain expressed X-linked 1 and neuronal pentraxin I, whose expression was significantly upregulated in combination-treated tumors compared with tumors treated with the two monotherapies.
conclusionsThese studies provide strong preclinical justification for combining imatinib mesylate with an AKT inhibitor as a front-line therapy in GIST. In addition, the WTS implicated the BCL-2/BAX/BAD apoptotic pathway as a potential mechanism for this enhanced combination effect. Clin Cancer Res; 23(1); 171-80. ©2016 AACR.
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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.