Combined-Modality Strategy for Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumor (GIST) is the most common nonepithelial tumor of the gastrointestinal tract. The majority of these tumors stain positive for the CD117 antigen to the KIT protein and have become a well-documented clinical entity. The dysregulated KIT protein is oncogenic and is an ideal target for imatinib, a KIT-selective inhibitor. Clinical trials of imatinib for metastatic GIST have shown either partial response or long-duration stable disease in 82% of patients. Trials addressing the efficacy of adjuvant imatinib following resection for high-risk primary GIST are awaiting results. The neoadjuvant preoperative use of imatinib to provide pharmacologic debulking and long-term disease control is also nearing completion in a clinical trial. This trial has the potential of addressing whether the combination of surgery and imatinib can enhance organ sparing, decrease drug resistance, and prolong disease-free and overall survival. The continued study of combining surgery and a target-specific agent for malignant GIST will be a valuable reference for future strategies combining surgery and targeted treatment in other solid tumors.