title: Gastrointestinal stromal tumors.
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.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University and Portland Veterans Affairs Medical Center, MC OP28, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201, USA. blankec@ohsu.edu
authors.forename: C D
authors.initials: CD
authors.lastname: Blanke
authors.forename: B L
authors.initials: BL
authors.lastname: Eisenberg
authors.forename: M C
authors.initials: MC
authors.lastname: Heinrich
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004812:Epidemiologic Methods; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000628:therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007167:Immunotherapy; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D009372:Neoplasms, Connective Tissue / Q000453:epidemiology / Q000628:therapy*; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011743:Pyrimidines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit