Targeting the molecular pathophysiology of gastrointestinal stromal tumors with imatinib - Mechanisms, successes, and challenges to rational drug development

The improved understanding of the molecular pathophysiology of gastrointestinal stromal tumors (GIST), a disease that was previously untreatable with any available systemic therapy, has led to the development of imatinib, a well-tolerated agent that can inhibit the dysregulated KIT signaling pathways in GIST. Imatinib represents the first (and currently the only) effective systemic therapy for patients with unresectable GIST. Imatinib therapy can induce objective responses and stabilization of disease and can provide clinical benefit in the majority of GIST patients treated with the drug. Other strategies are just beginning to be explored, such as the use of imatinib earlier the in course of GIST (eg, as adjuvant therapy after definitive surgical resection of early-stage disease). Integration of signal transduction inhibitors into the armamentarium of cancer therapeutics will undoubtedly continue based on this important paradigm of GIST.