@entity242 are @entity5 accounting for a high percentage of @entity5 morbidity and mortality in @entity1 and young adults. Surgery and radiation therapy are the accepted treatments for most @entity242 ; however, @entity1 with @entity3 are treated with systemic chemotherapy. Many @entity5 display marginal levels of chemoresponsiveness and new treatment approaches are needed. Deregulation of the G1 checkpoint is crucial for various oncogenic transformation processes, suggesting that many @entity5 cell types depend on @entity20405 activity. Thus, @entity20405 activity appears to represent a promising therapeutic target for @entity5 treatment. In the present work, we explore the efficacy of @entity8985 inhibition using palbociclib ( @entity20406 ), a highly selective inhibitor of @entity20405 , in a panel of @entity242 cell lines and @entity5 xenografts (PDXs). Palbociclib induces senescence in these cell lines and the responsiveness of these cell lines correlated with their levels of @entity8985 mRNA. @entity20406 is also active in vivo against @entity242 displaying high levels of @entity8985 but not against @entity242 displaying low levels of @entity8985 and high levels of @entity986 . The analysis of @entity5 growing after @entity20406 showed a clear decrease in the @entity8985 levels, indicating that clonal selection occurred in these treated @entity5 . In summary, our data support the efficacy of @entity8985 inhibitors against @entity242 displaying increased @entity8985 levels, particularly @entity1492 and @entity808 . Our results also suggest that high levels of @entity986 may indicate poor efficacy of @entity8985 inhibitors.

Efficacy of @entity8985 inhibition against @entity242 depends on their levels of XXXX and @entity986 mRNA.

@entity1 :: ('9606', 'Species') :: ['children', 'patients'] @entity20405 :: ('1019;1021', 'Gene') :: ['CDK4/6'] @entity808 :: ('MESH:D009442', 'Disease') :: ['MPNST'] @entity242 :: ('MESH:D012509', 'Disease') :: ['sarcoma', 'sarcomas', 'Sarcomas'] @entity986 :: ('1029', 'Gene') :: ['p16ink4a'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors', 'sarcoma tumor', 'malignant tumors', 'cancer'] @entity8985 :: ('1019', 'Gene') :: ['CDK4'] @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcomas'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic disease'] @entity20406 :: ('MESH:C500026', 'Chemical') :: ['Palbociclib', 'PD0332991', 'palbociclib']
@entity8985 :: (1019,Gene) :: ['CDK4']
