Treatment of a Patient With Metastatic Gastrointestinal Stromal Tumor
Release Date: February 5, 2009
Expiration Date: February 5, 2010
The management of gastrointestinal stromal tumor (GIST) was markedly changed several years ago by scientific and clinical evidence supporting the integration of kinase-targeted agents into the treatment armamentarium. The management of GIST continues to evolve, with new indications for and clinical trial data on kinase-targeted and other biologic agents. The utilization of molecular assessments to identify patients at high risk of recurrence and to personalize their treatment regimen is becoming an integral part of the management of patients with both resectable and advanced disease. The need for standards in patient selection is underscored by the recent approval of kinase-targeted therapy for patients with resectable KIT+ disease.
The purpose of this activity is to update physicians on current standards regarding devising treatment strategies including kinase-targeted agents based on gross and molecular disease characteristics in patients with KIT+ GIST.
This educational activity is intended for medical oncologists involved in the care of patients with GIST. No specific skills or knowledge other than a basic training in oncology is required for successful participation in this activity.
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Successful completion is determined by a score of 65% or greater.
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Charles D. Blanke, MD, FACP, FRCPC
Research Funding – Novartis Pharmaceuticals Corporation
Paid Consultant – Genentech, Inc.; Oncothyreon Inc.; Roche Pharmaceuticals; sanofi-aventis U.S.
PER Editorial Staff
Erin Grothey, MS (spouse)
Research Funding – Genentech, Inc.; sanofi-aventis U.S.
Paid Consultant – Amgen; Bayer Pharmaceuticals Corporation; Bristol-Myers Squibb Company; Genentech, Inc.; Roche Pharmaceuticals
Other PER Staff
No relevant relationships to disclose
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Activation of the c-KIT tyrosine kinase receptor requires receptor dimerization induced by the binding of stem cell factor, its ligand. Receptor dimerization results in autophosphorylation of distinct tyrosine residues present in the intracellular region of the receptor, which then bind various signaling proteins, such as Src family members and protein kinase C, to stimulate cell proliferation. The majority of gastrointestinal stromal tumors contain mutations that constitutively activate the c-KIT tyrosine kinase receptor. These mutations are frequently located in exon 11 (≈ 67%). Other activating mutations are found in exon 9 (≈ 9%), which encodes the dimerization motif, and, infrequently (≈ 1%), in exon 13 or exon 17, which code for the adenosine triphosphate binding site and activation loop motif of the kinase domain, respectively (Illustrator: Pam Curry).
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Editor, Interactive Case Study: Treatment of a Patient With Metastatic Gastrointestinal Stromal Tumor
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An educational grant for this activity was provided by:
Charles D. Blanke, MD, FACP, FRCPC
Systemic Therapy Provincial
Program Leader
British Columbia Cancer Agency
Head, Division of Medical Oncology
University of British Columbia
Vancouver, British Columbia, Canada