Considering the median PFS of IM-resistant GISTs harboring acquired secondary exon 17 mutation was noticeably shorter than that of patients with secondary exon 13/14 mutation, 2.3 months versus 7.8 months. Furthermore, Cauchi et al. found that the IM/SU-resistant GISTs of the only patient with prolonged disease stabilization after 3rd-line nilotinib also harbored exon 11/17 double mutation. In a phase II trial of 3rd-line dasatinib in IM/SUresistant GISTs, Trent et al. found that patients with PDGFRAAsp842Val mutated GISTs could achieve a U0126 better PFS than those with primary KIT mutated tumors. Unfortunately, the genotyping of GIST resistant to IM and SU was not available in the report of 3rd-line sorafenib trials. Taken together, these LY2157299 evidences support our findings that nilotinib may be a better agent for IM-resistant GIST with secondary exon 17 mutation than SU. Furthermore, we also introduced molecular modeling to elucidate the interaction between TKIs and mutant KIT proteins. Previous study of Mol et al. first resolved the crystal structure of KIT and its phosphorylation status. The molecular modeling of Mahadevan et al. showed that IM could not bind to Val654Ala mutant and explained the impact of KIT mutations on IM resistance. In this study, we found that nilotinib had the best binding affinity for exon 11/17, which is in consistent with our in vitro inhibitory efficacy study on KIT mutants. In recent decades, esophageal and gastro-esophageal junction cancer has seen a dramatic rise in incidence in developed countries while the five-year survival remains low at 19%. Identifying methods to select appropriate drug therapies are therefore warranted. Traditionally, cell line panels have been used to rapidly test anti-cancer agents. In addition, injections of cell lines into immunocompromised mice are common in vivo models of drug efficacy. Although cell line approaches have greatly contributed to drug development and cancer biology, they are imperfect models for drug testing. Furthermore, three widely used E/GEJ cancer cell lines were recently found to have been contaminated by other cell lines early in culture. Thus, idetifying appropriate pre-clinical drug-testing models of this cancer is a challenge. Primary tumor xenografts show promise as alternative pre-clinical models for drug sensitivity testing. PTXGs are created by implanting a piece of tumor directly from a patient into immunocompromised mice and using the resultant xenograft for experimentation. Primary tumor xenograft models of lung, breast, colon, head and neck and E/ GEJ cancers have been shown to recapitulate the patient tumor histology and cell morphology to varying degrees. Physiological conditions such as temperature, oxygen levels, nutrient content etc. more closely resemble those present in cancer patients. In addition, PTXGs have not undergone the selection pressures and significant molecular changes involved in cell line establishment and long-term growth,. Thus, PTXGs might be more likely to predict drug responses than cell lines grown either in vitro or in vivo.