Biomarkers for predicting response to XXXX kinase inhibitors in drug-sensitive and drug-resistant @entity1 @entity150 cells.

@entity1 @entity1366 @entity4562 @entity7514 @entity470 @entity9433 @entity21060 @entity584 @entity855 @entity876 @entity150 @entity1178 @entity669 @entity1722
The @entity470 ( @entity470 ) family is reportedly overexpressed in @entity150 , and @entity669 kinase inhibitors (TKIs) have been suggested as treatment. @entity4562 ( @entity4562  ) is a selective inhibitor of the @entity470 and @entity9433 is a dual inhibitor of both the @entity470 and @entity1722 ( @entity1 @entity470 type  2 receptor). Both compounds compete with the binding of @entity855 to the @entity669 kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical issue. The purpose of the present study was to use protein array analysis to compare the signaling pathway(s) induced by @entity4562 and @entity9433 , in UM-UC-5 (drug-sensitive) and UM-UC-14 (drug-resistant) @entity150 cells and to identify molecular markers that may be useful predictors of their efficacy. The results revealed that phosphorylation of @entity470 , @entity7514 , Met and @entity1366 was markedly overexpressed in the sensitive cell line (UM-UC-5) and was strongly inhibited by the TKIs. Other notable differences included decreased phosphorylation of RSK, GSK3, @entity21060 , @entity584 and @entity1178 by TKIs in the sensitive cells. In contrast, phosphorylated @entity876 was highly expressed in the resistant cell line (UM-UC-14) and TKIs had no effect in the resistant cells. Overall results suggest that phosphorylated @entity7514 , @entity1366 and @entity876 may be used as biomarkers to determine the sensitivity of @entity150 to TKIs. In particular, a combination of these markers may be more likely to predict the sensitivity to TKIs.
