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Is exon mutation analysis needed for adjuvant treatment of gastrointestinal stromal tumor?

World Journal of Gastroenterology 2013年第1期19卷 144-146页

作者： Mehmet Ali Nahit Sendur Nuriye Yildirim zdemir Muhammed Bülent Akinci Dogan Uncu Nurullah Zengin Sercan Aksoy Department of Medical Oncology Ankara Numune Education and Research HospitalAnkara 06100Turkey Department of Medical Oncology Hacettepe University Institute of OncologyAnkara 06100Turkey

Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) *** GISTs(90%-95%) are *** 5% of GISTs are truly negative for KIT *** have been documented to resistant conventional *** to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic *** mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ *** presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic *** analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase *** aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.

关键词： Imatinib Gastrointestinal stromal tumor Activating mutation Stem cell factor receptor platelet-derived growth factor receptor alpha Mutation analysis

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Therapeutic targets in gastrointestinal stromal tumors

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World Journal of Translational Medicine 2015年第1期4卷 25-37页

作者： Jia-Qing Zhu Wen-Bin Ou College of Life Sciences Zhejiang Sci-Tech University Zhejiang Provincial Key Laboratory of Applied Enzymology Yangtze Delta Region Institute of Tsinghua University

Gastrointestinal stromal tumors(GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The tumorigenesis of GISTs is driven by gain-of-function mutations in KIT or plateletderived growth factor receptor α(PDGFRA),resultingin constitutive activation of the tyrosine kinase and its downstream signaling pathways. Oncogenic KIT or PDGFRA mutations are compelling therapeutic targets for the treatment of GISTs,and the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GISTs. However,most GIST patients develop clinical resistance to imatinib and other tyrosine kinase inhibitors. Five mechanisms of resistance have been characterized:(1) acquisition of a secondary point mutation in KIT or PDGFRA;(2) genomic amplification of KIT;(3) activation of an alternative receptor tyrosine kinase;(4) loss of KIT oncoprotein expression; and(5) wild-type GIST. Currently,sunitinib is used as a secondline treatment for patients after imatinib failure,and regorafenib has been approved for patients whose disease is progressing on both imatinib and sunitinib. Phase Ⅱ/Ⅲ trials are currently in progress to evaluate novel inhibitors and immunotherapies targeting KIT,its downstream effectors such as phosphatidylinositol 3-kinase,protein kinase B and mammalian target of rapamycin,heat shock protein 90,and histone deacetylase inhibitor. Other candidate targets have been identified,including ETV1,AXL,insulin-like growth factor 1 receptor,KRAS,FAS receptor,protein kinase c theta,ANO1(DOG1),CDC37,and aurora kinase A. These candidates warrant clinical evaluation as novel therapeutic targets in GIST.

关键词： Gastrointestinal stromal tumors Tyrosine kinase inhibitors KIT platelet-derived growth factor receptorα Targets

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Behavior of advanced gastrointestinal stromal tumor in a patient with von-Recklinghausen disease: Case report

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World Journal of Clinical Oncology 2013年第3期4卷 70-74页

作者： Samer Sawalhi Khalid Al-Harbi Zakaria Raghib Abdelrahman I Abdelrahman Ahmed Al-Hujaily Department of Surgery Permanent researcher in the Centre of Genetics and Inherited DiseasesCollege of Medicine-Taibah UniversityAl-Madina 30001Saudi Arabia Center of Genetics and Inherited Diseases College of MedicineTaibah UniversityAl-Madina 30001Saudi Arabia Department of Surgery King Fahd HospitalAl-Madina 42351Saudi Arabia Department of Radiology King Fahd HospitalAl-Madina 42351Saudi Arabia Department of Pathology King Fahd HospitalAl-Madina 42351Saudi Arabia

Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen *** the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight *** employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene ***,the patient was given Imatinib mesylate(Gleevec)as adjuvant *** scan delineated a large thick wall cavity lesion connecting to the small bowel *** of the tumor yielded a mass of 17 cm×13 cm with achievement of safety *** diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and *** revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST ***,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our *** our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.

关键词： KIT Gastrointestinal stromal tumor Imatinib Neurofibromatosis type-1 platelet-derived growth factor receptor-alpha

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