Activation of FGFR signaling through mutations, amplifications, or fusions involving @entity7167 , 2, 3, or 4 is seen in @entity5 , including lung, bladder, and @entity201 . Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid @entity5 . As we move forward with FGFR inhibitors clinically, we anticipate the emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated @entity5 cell lines. We identified @entity5 cell lines that have activating mutations in @entity7167 , 2, or 3 and treated them chronically with the selective FGFR inhibitor, @entity40617 . We observed resistance to chronic @entity40617 exposure in @entity1 ( @entity151 , @entity7167 amplification) and RT112 ( @entity189 , @entity2557 fusion/amplification) cell lines based on viability assays. Reverse-phase protein array (RPPA) analysis showed increased phosphorylation of @entity584 (T308 and S473) and its downstream target GSK3 (S9 and S21) in both the resistant cell lines when compared with matching controls. Results of RPPA were confirmed using immunoblots. Consequently, the addition of an @entity584 inhibitor ( @entity69413 ) or siRNA was able to restore sensitivity to @entity40617 in resistant cell lines. These data suggest a role for @entity584 pathway in mediating acquired resistance to FGFR inhibition. Mol Cancer Ther; 1-11.   2017 AACR.

XXXX Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor @entity40617 .

@entity1 :: ('9606', 'Species') :: ['DMS114'] @entity40617 :: ('MESH:C568950', 'Chemical') :: ['BGJ398'] @entity5 :: ('MESH:D009369', 'Disease') :: ['multiple tumors', 'cancer', 'tumors'] @entity2557 :: ('2261', 'Gene') :: ['FGFR3'] @entity189 :: ('MESH:D002277', 'Disease') :: ['urothelial carcinoma'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity201 :: ('MESH:D018281', 'Disease') :: ['cholangiocarcinoma'] @entity69413 :: ('MESH:C000595149', 'Chemical') :: ['GSK2141795'] @entity151 :: ('MESH:D055752', 'Disease') :: ['small-cell lung cancer'] @entity7167 :: ('2260', 'Gene') :: ['FGFR1']
@entity584 :: (207,Gene) :: ['Akt']
