BACKGROUND: Increased expression of the @entity470 ( @entity470 ) is observed in more than 90% of all @entity213 ( @entity213 ). Therefore, @entity470 has emerged as a promising therapeutic target. Nevertheless, drug resistance remains a major challenge and an important potential mechanism of drug resistance involves the @entity5 microenvironment. Therefore, we investigated the cytotoxic effect of the @entity470 -targeting agents cetuximab and @entity3866 under normoxia versus @entity519 . FINDINGS: Three cetuximab-sensitive @entity213 cell lines (SC263, LICR-HN2 and LICR-HN5) were treated with either cetuximab or @entity3866 . Cells were incubated under normal or reduced @entity26 conditions (<0.1% @entity3612 ) for 24 or 72  h immediately after drug addition. Cell survival was assessed with the @entity7664 assay. Cetuximab and @entity3866 established a dose-dependent growth inhibition under both normal and prolonged reduced @entity26 conditions in all three @entity213 cell lines. However, a significantly increased sensitivity to cetuximab was observed in SC263 cells exposed to @entity519 for 72  h (p  =  0.05), with IC50 values of 2.38      0.59  nM, 0.64      0.38  nM, and 0.10      0.05  nM under normoxia, @entity519 for 24   h and @entity519 for  72  h, respectively. LICR-HN5 cells showed an increased sensitivity towards @entity3866 when cells were incubated under @entity519 for 24  h (p  =  0.05). CONCLUSIONS: Our results suggest that both @entity470 -inhibitors cetuximab and @entity3866 maintain their growth inhibitory effect under @entity519 . These results suggest that resistance to anti- @entity470 therapy in @entity213 is probably not the result of @entity519 regions within the @entity5 and other mechanisms are involved.

The @entity5 microenvironment and drug resistance against XXXX inhibitors: preclinical study in cetuximab-sensitive head and @entity213 cell lines.

@entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'hypoxic tumor'] @entity213 :: ('MESH:C535575', 'Disease') :: ['HNSCC', 'head and neck squamous cell carcinomas'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity7664 :: ('CHEBI:52101', 'Chemical') :: ['sulforhodamine B'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia', 'hypoxic'] @entity3612 :: ('D013481', 'Chemical') :: ['O2'] @entity3866 :: ('MESH:C400278', 'Chemical') :: ['erlotinib']
@entity470 :: (1956,Gene) :: ['EGFR']
