A clinical and biological overview of gastrointestinal stromal tumors
Por:
Candelaria M., De La Garza J., Duenas-Gonzalez A.
Publicada:
1 ene 2005
Resumen:
In the last few years a body of knowledge has been generated on the molecular basis of gastrointestinal stromal tumors (GIST). These mesenchymal tumors are characterized by the expression of KIT protein and because they have an activating mutation in a class III receptor tyrosine kinase gene (KIT or PDGFRA). Several KIT-activating mutations, which are largely responsible for the development of this tumor, promote cell survival, proliferation, and migration through different pathways such as MAPK p42/44, AKT, S6K, STAT1, and STAT3. Likewise, gene-activating mutations in the gene PDGFR? which codes for the receptor tyrosine kinase, Platelet-derived growth factor receptor ? have been identified in GIST lacking KIT mutations. This means that KIT and PDGFR? mutations appear to be alternative and mutually exclusive oncogenic pathways for GIST development. These tumors may occur anywhere along the gastrointestinal tract (GI). The most frequently involved sites are stomach and small intestine. They are typically chemo- and radioresistant. The discovery of a specific inhibitor of this tyrosine kinase, imatinib mesylate, has radically changed the prognosis of patients with unresectable disease. Only 4 yr after the first patient was successfully treated with imatinib, multiple phase II and III trials have been published and, currently, imatinib mesylate is the only effective systemic treatment available of these tumors. Response rates are approximately 70-90% with acceptable toxicity. GIST are the first model of a solid tumor efficiently treated with a molecular-targeted agent. This review summarizes the clinical and biological aspects of this unique neoplasm. © Copyright 2005 by Humana Press Inc. All rights of any nature whatsoever reserved.
Filiaciones:
Candelaria M.:
Division of Clinical Research, National Cancer Institute, Mexico City, Mexico
Department of Clinical Research, National Cancer Institute, Mexico, Ave. San Fernando 22, Tlalpan, CP 14080, Mexico City, Mexico
De La Garza J.:
Division of Clinical Research, National Cancer Institute, Mexico City, Mexico
Duenas-Gonzalez A.:
Unit of Biomedical Research on Cancer, Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City, Mexico
National Cancer Institute of Mexico, Mexico City, Mexico
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