Abstract:In the last decade a tremendous amount has been learned about the biology and treatment of gastrointestinal stromal tumor (GIST). Imatinib mesylate has revolutionized the treatment of metastatic GIST. In addition, the role of imatinib in localized GIST has gained much interest and may improve patient outcomes. Additionally, research efforts aimed at understanding the biology and the molecular heterogeneity of GIST both at initial presentation and at the time of resistance to imatinib, has helped guide rational approaches to treatment as well as future efforts aimed at treating imatinib-resistant GIST. Keywords: gastrointestinal stromal tumors, GIST, review, imatinib, tyrosine kinase inhibitor, TKI
DiagnosisGastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract.1 As a distinct disease entity, it is estimated that GIST has an annual incidence of around 14.5 per million individuals worldwide.2 The median age of onset is ∼60 years old with a small though biologically distinct sub-population in the pediatric age group. 3,4 Prior to the late 1990s, GIST was a disease poorly understood, whose pathogenesis, natural history and even the cell of origin were unclear. In addition, GISTs were frequently diagnosed as other entities, which included leiomyosarcoma, leiomyoblastoma, bizarre leiomyoma, plexosarcoma and gastrointestinal autonomic nerve tumor (GANT) amongst other names. 5,6 It was not until the seminal discovery by Hirota and colleagues in 1998 that the first clear insights to this disease were gained. In this landmark publication, the group reported the finding of activating KIT mutations in a significant proportion of GISTs, with constitutive ligand-independent activation of the KIT-receptor tyrosine kinase (RTK), and a near universal expression of KIT on immunohistochemistry.7 Corroborated by Kindblom and others, it was demonstrated that GIST cells were closely related to the interstitial cells of Cajal.8 This understanding provided the platform for accurate and uniform diagnoses of this uncommon tumor and the rational development and use of tyrosine kinase inhibitors (TKI) in the management of GIST.
Prognostic factorsAs it became clearer investigators could reliably identify GIST, research efforts were focused on the determination of histological and clinical prognostic factors Biologics: Targets and Therapy downloaded from https: //www.dovepress.com/ by 34.213.178.48 on 11-May-2018 For personal use only.