This is typically due to secondary KIT mutations within the kinase domain by either interfering with drug binding within the ATP-binding domain (exon 13/14 mutations) or b modifying the activation loop to stabilize the active conformation (exon 17/18 mutations).23,26,48-51Figure 1 shows the current understanding of primary and secondary resistance to select TKIs in KIT or PDGFRA mutant GIST. This evidence concerns the gene KIT and gastrointestinal stromal tumor.