Implications of mutational analysis for the management of patients with gastrointestinal stromal tumors and the application of targeted therapies.
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.
Wozniak
Agnieszka
A
Department of General Medical Oncology and Laboratory of Experimental Oncology, University Hospital Gasthuisberg, Leuven, Belgium. Agnieszka.Wozniak@med.kuleuven.be
Floris
Giuseppe
G
Debiec-Rychter
Maria
M
Sciot
Raf
R
Schöffski
Patrick
P
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011758:Pyrroles / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D018570:Risk Assessment; D000077210:Sunitinib; D015533:Transcriptional Activation
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000077210:Sunitinib