Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KIT AY502-3ins mutation: An in vitro mutagenesis screen for drug resistance
Drug Resistance, Neoplasm
Gastrointestinal Stromal Tumors
Proto-Oncogene Proteins c-kit
Sunitinib resistance in GIST shares similar pathogenetic mechanisms identified in imatinib failure, with acquisition of secondary mutations in the activation domain after an extended initial response to the drug. Moreover, in vitro mutagenesis with or without N-ethyl-N-nitrosourea of Ba/F3 cells expressing KIT(AY502-3ins) showed acquisition of secondary mutations restricted to the second kinase domain of KIT. In contrast, in vitro resistance to imatinib produces a broader spectrum of secondary mutations including mutations in both KIT kinase domains.