Clinical management of gastrointestinal stromal tumors: before and after STI-571.

Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G
Hum Pathol. 2002 33 (5): 466-77

PMID: 12094371 · DOI:10.1053/hupa.2002.124122

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Until recently, surgery has been the only effective therapy for GIST. However, even after complete resection of tumor, many patients still eventually die of disease recurrence. Conventional chemotherapy and radiation therapy have been of limited value. Within the last few years, it was discovered that most GISTs have a gain-of-function mutation in the c-kit proto-oncogene. This results in ligand-independent activation of the KIT receptor tyrosine kinase and an unopposed stimulus for cell growth. STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Its clinical development marks a new era of rational and targeted molecular inhibition of cancer that emanates from direct collaborations between scientists and clinicians. It provides proof of the principle that a specific molecular inhibitor can drastically and selectively alter the survival of a neoplastic cell with a particular genetic aberration. The advent of STI-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy.

Copyright 2002, Elsevier Science (USA). All rights reserved.

MeSH Terms (22)

Adult Aged Aged, 80 and over Antineoplastic Agents Benzamides Biomarkers, Tumor Chemotherapy, Adjuvant Female Gastrointestinal Neoplasms Humans Imatinib Mesylate Male Middle Aged Mutation Piperazines Proto-Oncogene Proteins c-kit Pyrimidines Sarcoma Sarcoma Stromal Cells Survival Analysis Survival Rate

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