INTRODUCTION: Chemoresistance is a major challenge in the treatment of advanced @entity1149 ( @entity1149 ). Because the Sonic hedgehog ( @entity4851 ) pathway is reactivated in @entity1149 , we investigated an association between chemoresistance and @entity4851 activation. @entity1 AND METHODS: From a cohort of 178 @entity1 with advanced @entity1149 treated with @entity902 -based chemotherapy as first-line treatment, we selected all surgical @entity5 samples at diagnosis (n  = 36). @entity4851 activation was evaluated through @entity8889 and @entity1357 expression using immunohistochemistry (quantitative score). In  vitro treatment studies with @entity900 or @entity2752 ( @entity4851 pathway inhibitor), or both, were performed on @entity1149 cell lines (H322 and A549) and primary cultures from @entity1 with @entity189 (n  =  4). RESULTS: Of the 36 @entity1 , 12 had @entity1149 refractory to chemotherapy (R- @entity1 , 33.3%) and 24 had controlled disease (C- @entity1 ). @entity8889 expression did not differ between the R- and C- @entity1 (P  = .35). @entity1357 expression was more often positive in the R- @entity1 (41.7% vs. 8.3%; P  = .02). Progression-free survival (PFS) and @entity1349 ( @entity1349 ) in @entity1 with a @entity1357 -positive score was 2.1 and 8.0 months, respectively, compared with 6.7 and 18.0 months for @entity1 with a @entity1357 -negative score (P  = .03 and P  = .002, respectively). On multivariate analysis, the @entity1357 score correlated independently with PFS (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.05-6.63; P  = .04) and @entity1349 (HR, 4.36; 95% CI, 1.67-11.36; P  = .003). The @entity189 cell lines were more resistant to @entity900 than were the H838 and A549 cell lines. The @entity900 -vismodegib combination displayed a synergistic cytotoxic effect  in the most chemoresistant cells in  vitro. CONCLUSION: The @entity4851 pathway is associated with resistance to @entity902 -based chemotherapy in @entity1149 .

Sonic Hedgehog Pathway Activation Is Associated With Resistance to XXXX -Based Chemotherapy in Advanced @entity1149 .

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity1357 :: ('2736', 'Gene') :: ['Gli2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity189 :: ('MESH:D002277', 'Disease') :: ['sarcomatoid carcinoma'] @entity8889 :: ('2735', 'Gene') :: ['Gli1'] @entity4851 :: ('6469', 'Gene') :: ['Shh'] @entity2752 :: ('MESH:C538724', 'Chemical') :: ['vismodegib'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival']
@entity902 :: (MESH:D010984,Chemical) :: ['Platinum']
