Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KIT AY502-3ins mutation: An in vitro mutagenesis screen for drug resistance Academic Article uri icon

Overview

MeSH Major

  • Drug Resistance, Neoplasm
  • Gastrointestinal Stromal Tumors
  • Indoles
  • Mutation
  • Proto-Oncogene Proteins c-kit
  • Pyrroles

abstract

  • 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.

publication date

  • November 15, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2783687

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-09-1315

PubMed ID

  • 19861442

Additional Document Info

start page

  • 6862

end page

  • 70

volume

  • 15

number

  • 22