Establishment of genetically diverse @entity1 -derived xenografts of XXXX .

@entity1 @entity19 @entity5 @entity8839 @entity3470 @entity4706 @entity14
Preclinical compounds tested in animal models often show limited efficacy when transitioned into @entity1 clinical trials. As a result, many @entity1 are stratified into treatment regimens that have little impact on their disease. In order to create preclinical models that can more accurately predict @entity5 responses, we established @entity1 -derived xenograft (PDX) models of @entity14 ( @entity14 ). Surgically resected @entity5 specimens from @entity14 @entity1 were implanted subcutaneously into athymic @entity19 . Following successful establishment, fourteen models underwent further evaluation to determine whether these models exhibit heterogeneity, both at the cellular and genetic level. Histological review revealed properties not found in @entity14 cell lines, most notably in overall architecture (predominantly columnar epithelium with evidence of gland formation) and the presence of mucin-producing cells. Custom @entity14 gene panels identified somatic driver mutations in each model, and therapeutic efficacy studies in @entity5 -bearing @entity19 were designed to determine how models with known mutations respond to PI3K, @entity3470 , or MAPK inhibitors. Interestingly, MAPK pathway inhibition drove @entity5 responses across most models tested. Noteworthy, the MAPK inhibitor @entity8839 alone did not significantly mediate @entity5 response in the context of a KRAS( @entity4706 ) model, and improved @entity5 responses resulted when combined with @entity3470 inhibition. As a result, these genetically diverse models represent a valuable resource for preclinical efficacy and drug discovery studies.
