[Gastrointestinal stromal tumors (GIST)]

Area of Science:

• Gastrointestinal oncology
• Molecular pathology
• Medical therapeutics

Context:

• Gastrointestinal stromal tumors (GIST) represent the majority of mesenchymal tumors in the GI tract.
• GIST incidence is 10-20/million, median age 55-65 years, commonly in stomach/duodenum.
• Metastatic disease at diagnosis occurs in about half of patients, primarily to the liver/peritoneum.

Purpose:

• To define the characteristics and treatment landscape of GIST.
• To highlight the role of c-kit mutations in GIST pathogenesis.
• To present early clinical trial results for imatinib in advanced GIST.

Summary:

• GISTs are characterized by uniform CD117 (c-kit) positivity, with mutations in c-kit driving pathogenesis.
• Imatinib (STI571) is an orally available tyrosine kinase inhibitor targeting c-kit.
• Clinical trials demonstrate high activity of imatinib, with ~60% response rates and >80% progression arrest.

Impact:

• Imatinib offers a novel, active systemic treatment for advanced GIST, improving patient outcomes.
• Ongoing trials are evaluating adjuvant imatinib and novel strategies for imatinib-resistant disease.
• This research advances the understanding and management of a rare but significant gastrointestinal malignancy.