IGF-1R: A novel GIST therapeutic target
The vast majority of GISTs arising in adult patients have activating mutations of the KIT or PDGFRA genes (80- 90%). GISTs lacking activating KIT or PDGFRA mutations are commonly referred to as wild-type GIST. Despite intensive research, the molecular abnormalities giving rise to wild-type GISTs remain unknown. Compared to the common exon 11-mutant GISTs, wild-type GISTs have lower rates of objective response to imatinib. In addition, the progression free and overall survival of patients with wild-type GIST is reduced compared to that of patients with KIT exon 11-mutant GIST. In pediatric GIST, the kinase mutational frequency is reversed, with more than 90 percent of pediatric GIST having a wild-type genotype. Notably, the effectiveness of imatinib against wildtype pediatric GIST is often reduced compared with its activity against adult wild-type GIST.
