Update on the Biology and Therapy of Gastrointestinal Stromal
Update on the Biology and Therapy of Gastrointestinal Stromal
Background: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are an example of a disease with an effective, molecularly targeted therapy.
Methods: Published articles and author experience were used to comprehensively define the clinical features, biology, and state-of-the-art therapy of GISTs.
Results: GISTs are thought to originate from the neoplastic transformation of the interstitial cells of Cajal, the intestinal pacemaker cells. GISTs commonly have mutations in the kit gene, resulting in a gain-of-function mutation and ligand-independent constitutive activation of the KIT receptor tyrosine kinase. Successful tyrosine kinase inhibitors target the aberrant pathways that are critical for tumor cell viability. The development of imatinib mesylate (formerly STI 571) in the treatment of metastatic GISTs represents a therapeutic breakthrough.
Conclusions: Progress in the clinical diagnosis has led to an increased recognition of this disease as a distinct clinical entity. Treatment of metastatic GIST with imatinib has led to unprecedented improvements in progression-free and overall survival. The use of imatinib in the preoperative and postoperative treatment of GISTs is an area of intense investigation.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Over 85% of GISTs express the KIT receptor (stem cell factor receptor, CD117), as shown by immunohistochemical analysis. Approximately 60% of GISTs occur in the stomach, 25% in the small intestine, and 10% in the colon and rectum. The remainder arise from other sites in the GI tract or rare locations such as the gall bladder, appendix, omentum, or mesentery. However, GISTs account for approximately 2% of all stomach tumors, 14% of all small intestine tumors, and 0.1% of colon tumors. In the United States, the incidence is approximately 5,000 new cases annually. The median age at diagnosis is approximately 58 years. As early as the 1940s, GISTs were often diagnosed as smooth muscle tumors of the GI tract (GI leiomyosarcoma, leiomyoblastoma, and leiomyoma), but advances in histopathology later provided evidence that GISTs were distinct from the smooth muscle tumors.
Background: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are an example of a disease with an effective, molecularly targeted therapy.
Methods: Published articles and author experience were used to comprehensively define the clinical features, biology, and state-of-the-art therapy of GISTs.
Results: GISTs are thought to originate from the neoplastic transformation of the interstitial cells of Cajal, the intestinal pacemaker cells. GISTs commonly have mutations in the kit gene, resulting in a gain-of-function mutation and ligand-independent constitutive activation of the KIT receptor tyrosine kinase. Successful tyrosine kinase inhibitors target the aberrant pathways that are critical for tumor cell viability. The development of imatinib mesylate (formerly STI 571) in the treatment of metastatic GISTs represents a therapeutic breakthrough.
Conclusions: Progress in the clinical diagnosis has led to an increased recognition of this disease as a distinct clinical entity. Treatment of metastatic GIST with imatinib has led to unprecedented improvements in progression-free and overall survival. The use of imatinib in the preoperative and postoperative treatment of GISTs is an area of intense investigation.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Over 85% of GISTs express the KIT receptor (stem cell factor receptor, CD117), as shown by immunohistochemical analysis. Approximately 60% of GISTs occur in the stomach, 25% in the small intestine, and 10% in the colon and rectum. The remainder arise from other sites in the GI tract or rare locations such as the gall bladder, appendix, omentum, or mesentery. However, GISTs account for approximately 2% of all stomach tumors, 14% of all small intestine tumors, and 0.1% of colon tumors. In the United States, the incidence is approximately 5,000 new cases annually. The median age at diagnosis is approximately 58 years. As early as the 1940s, GISTs were often diagnosed as smooth muscle tumors of the GI tract (GI leiomyosarcoma, leiomyoblastoma, and leiomyoma), but advances in histopathology later provided evidence that GISTs were distinct from the smooth muscle tumors.
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