Implications of Mutational Analysis for the Management of Patients With Gastrointestinal Stromal Tumors and the Application of Targeted Therapies

ABSTRACT

The receptor tyrosine kinase inhibitors, imatinib and sunitinib, have significantly improved the prognosis for patients with advanced gastrointestinal stromal tumors (GISTs). Most GISTs exhibit mutations in the genes encoding the stem cell factor receptor (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Imatinib is more effective in patients with KIT exon 11 mutations compared with KIT exon 9 mutations and wild-type genotype, while sunitinib confers greater in vitro efficacy in patients with KIT exon 9 mutants and wild-type genotype than in KIT exon 11 mutants. This review examines the potential role of mutational analysis to optimize therapy with imatinib and sunitinib for GIST.

Keywords: :

• Gastrointestinal stromal tumor
• Mutational status
• KIT
• PDGFRA
• Targeted therapy
• Treatment resistance
• Imatinib mesylate
• Sunitinib malate

ACKNOWLEDGMENTS

The study was partially supported by the Connective Tissue Cancer Network of Excellence, (FP6-018806). Editorial assistance for this manuscript was provided by Cherry Bwalya at ACUMED (Tytherington, UK), with funding from Pfizer Inc.

Declaration of interest: A Wozniak, G Floris and R Sciot have no potential conflicts of interest to declare. P Schöffski has no potential conflict of interest with respect to this article. He has received research funding for translational and clinical research in GIST from the following companies: Novartis, Pfizer, Infinity. M Debiec-Rychter has received honoraria from Novartis.