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      Gastrointestinal stromal tumors.

      Current Treatment Options in Oncology

      Antineoplastic Agents, therapeutic use, Benzamides, Chemotherapy, Adjuvant, Combined Modality Therapy, Digestive System Surgical Procedures, Enzyme Inhibitors, Epidemiologic Methods, Gastrointestinal Neoplasms, epidemiology, therapy, Humans, Immunotherapy, Neoplasm Metastasis, Neoplasm Proteins, analysis, antagonists & inhibitors, Neoplasm Recurrence, Local, surgery, Neoplasms, Connective Tissue, Piperazines, Prognosis, Proto-Oncogene Proteins c-kit, Pyrimidines, Treatment Outcome, Tumor Markers, Biological

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are mesenchymal gut tumors that differ dramatically from other histologically similar neoplasms, such as leimomyomas, leiomyosarcomas (LMS), and neural tumors. Complete surgical removal remains the best current therapy for GISTs, but even major resections are associated with recurrence in approximately 90% of cases. GISTs are remarkably resistant to irradiation and standard chemotherapy; there is no role for treatment with those modalities. Treatment of advanced GIST patients with STI571, a novel selective tyrosine kinase inhibitor, results in remission rates that approach 60% and overall tumor control rates of 85%. Selected groups of patients, as based on tumor mutational status, have response rates as high as 80%. To date, STI571 therapy remains the only systemic treatment for GISTs to have meaningful clinical activity. Though other molecularly targeted therapies exist in oncology (eg, trastuzumab), STI571 is one of the first that applies a drug specifically designed to inhibit the product of a constitutively-activating mutation that drives pathogenesis of a solid tumor. Its use can serve as a paradigm for designing molecularly targeted therapies for other malignancies.

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          12057094

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