UNASSIGNED: The treatment of @entity463 ( @entity463 ) remains challenging in part due to the presence of stem-like @entity5 -propagating cells that are resistant to standard therapies consisting of radiation and @entity2903 . Among the novel and targeted agents under evaluation for the treatment of @entity463 are @entity817 /MAPK inhibitors, but their effects on @entity5 -propagating cells are unclear. Here, we characterized the behaviors of @entity5439 (+) @entity5 -propagating cells isolated from primary @entity463 cell lines. We show that @entity5439 (+) cells exhibited decreased sensitivity to the antiproliferative effects of @entity817 /MAPK inhibition compared to @entity5439 (-) cells. Furthermore, @entity5439 (+) cells exhibited an extended G2-M phase and increased polarized asymmetric cell divisions. At the molecular level, we observed that polo-like kinase ( @entity9370 activity was elevated in @entity5439 (+) cells, prompting our investigation of @entity817 / @entity9370 combination treatment effects in an orthotopic @entity463 xenograft model. Combined inhibition of @entity817 and @entity9370 resulted in significantly greater antiproliferative and proapoptotic effects beyond those achieved by monotherapy (P < 0.05). We propose that @entity9370 activity controls a polarity checkpoint and compensates for @entity817 /MAPK inhibition in @entity5439 (+) cells, suggesting the need for concurrent @entity9370 inhibition to improve antitumor activity against a therapy-resistant cell compartment. @entity5 Res; 75(24); 5355-66.   2015 AACR.

Targeting a XXXX -Controlled Polarity Checkpoint in Therapy-Resistant @entity463 -Propagating Cells.

@entity5439 :: ('8842', 'Gene') :: ['CD133'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Cancer'] @entity9370 :: ('5347', 'Gene') :: ['PLK) 1', 'PLK1'] @entity2903 :: ('MESH:C047246', 'Chemical') :: ['temozolomide'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity463 :: ('MESH:D005909', 'Disease') :: ['GBM', 'glioblastoma']
@entity9370 :: (5347,Gene) :: ['Plk1']
