Abstract A13: Establishment and characterization of patient-derived xenograft models of gastrointestinal stromal tumor resistant to standard tyrosine kinase inhibitors

BACKGROUND : The prognosis of gastrointestinal stromal tumor (GIST) has been dramatically improved after introduction of imatinib which can inhibit the driver mutated oncoproteins, KIT or PDGFRa . However, most patients eventually develop resistance to the tyrosine kinase inhibitors (TKIs) targeting these oncoproteins including imatinib, sunitinib, or regorafenib. The paucity of TKIs-resistant commercially available GIST cell lines hampers development of effective therapy for drug-resistant GIST. Therefore, we established patient-derived xenograft (PDX) models that faithfully recapitulate the genetic and phenotypic features of drug-resistant GIST. METHODS : PDXs have been established in NOD-SCID mice with tumor fragments of patients with metastatic and/or unresectable GIST after failure of at least imatinib and/or sunitinib. The histological and genomic similarities between all xenografts and the parental tumors have been confirmed using HE 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A13.