Gastrointestinal stromal tumors: a spectrum of disease.

The majority of gastrointestinal stromal tumors (GIST) express c-kit, a growth factor receptor with tyrosine kinase activity. Mutations in the c-kit proto-oncogene may lead to constitutive ligand-independent activation of c-kit and subsequent neoplastic transformation. Selective tyrosine kinase inhibitors target this property of GIST and have become the standard chemotherapy for metastatic or unresectable tumors. The mainstay of treatment, however, continues to be complete surgical resection. Tyrosine kinase inhibitors may prove expedient for adjuvant therapy, and are currently the focus of clinical trials conducted by the ACOSOG, RTOG, and ACRIN. It is important to distinguish GISTs from other mesenchymal tumors of the GI tract because of differences in natural history, as well as the efficacy of treatments targeting the GIST tyrosine kinase.