Response to @entity4562 and XXXX in @entity1149 : a restrospective study.

@entity1 @entity4562 @entity1910 @entity470 @entity5 @entity1149 @entity7952 @entity669 @entity1054 @entity3866
BACKGROUND: In @entity1149 ( @entity1149 ), an overactive @entity470 ( @entity470 ) pathway is a component of the malignant phenotype. Two @entity669 kinase inhibitors (TKIs) of @entity470 , gefinitib and @entity3866 , have been used with variable benefit. METHODS: We have analyzed outcome data of a population of @entity1149 @entity1 that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response. @entity5 tissue from a subgroup of these @entity1 was analyzed by immunohistochemistry to measure the expression level of @entity470 and four activated (phosphorylated) members of the pathway, pEGFR, @entity7952 , pAKT, and pSTAT3. RESULTS: @entity3866 was slightly superior to @entity4562 in all measures of response, although the differences were not statistically significant. The most robust clinical predictors of @entity1054 ( @entity1054 ) were best response and @entity1910 (p < 0.0001). A higher level of pEGFR was associated with longer @entity1054 , while the total @entity470 level was not associated with response. Higher levels of pAKT and pSTAT3 were also associated with longer @entity1054 . In contrast, a higher level of pERK1/2 was associated with shorter @entity1054 . CONCLUSION: These observations suggest the hypothesis that @entity5 cells that have activated @entity470 pathways, presumably being utilized for survival, are clinically relevant targets for pathway inhibition. An accurate molecular predictive model of TKI response should include activated members of the @entity470 pathway. TKIs may be best reserved for @entity5 expressing pEGFR and pAKT or pSTAT, and little @entity7952 . In the absence of molecular predictors of response, the appearance of a @entity1910 and a positive first scan are good clinical indicators of response.
