Even though imatinib is highly effective in the first line, and up to 30% have remained progression-free after 5 years and 7 to 9% after 10 years [84,85], the great majority of patients will develop disease resistance and acquired secondary mutations in KIT or PDGFRA, which constitutes the main mechanism of failure to imatinib in 70 to 90% of GIST patients. This evidence concerns the gene PDGFRA and gastrointestinal stromal tumor.