UNASSIGNED: 150 Background: @entity263 ( @entity263 ) is one of the leading causes of @entity204 from @entity5 in @entity1 . High Gleason grade prostate @entity5 are characterized by @entity146 with poorly differentiated cells and a high metastatic potential. They are often refractory to chemical castration but still treated with hormone therapy to which @entity1205 or @entity15513 are added when they become resistant to the anti- @entity342 . Despite many clinical trials with other chemotherapeutic agents, response rates remain low. Moreover, none of these trials took into account the @entity5 grade. METHODS: We used an in silico approach to screen for drug candidates that could be used as an alternative to @entity6023 , based on a 86 genes signature which could distinguish between low-grade and high-grade @entity5 . We extracted from the NCI60 panel databases the expression profiles of the 86 genes across 60 @entity1 @entity5 cell lines and the corresponding in vitro cytotoxicity data of 152 drugs and looked for correlation between their expression level and cell sensitivity to each of these drugs. RESULTS: Among the 86 genes, we identified 9 genes ( @entity68827 , @entity68828 , @entity68829 , @entity68830 , @entity60955 , @entity1009 , @entity25521 , @entity30291 , @entity1178 ) for which expression levels across the 60 cell lines was significantly correlated (p< 0.05) to @entity901 but not to @entity900 sensitivity. This signature was validated at the functional level since repression of each of these genes conferred a significant change in the sensitivity of @entity263 cell lines to @entity901 but not @entity900 . CONCLUSIONS: Our results provide a proof of concept that gene expression signature specific from high grade @entity263 could be used for the identification of alternative therapies to @entity6023 . They could also be used to select @entity1 for further clinical trials and as predictive markers of response to these drugs, which represents a further step forward towards personalized therapy of @entity263 .

A gene expression signature to predict high-grade @entity263 response to XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'men', 'patients'] @entity25521 :: ('1973', 'Gene') :: ['EIF4AI'] @entity68828 :: ('6472', 'Gene') :: ['SHMT2'] @entity68830 :: ('89941', 'Gene') :: ['RHOT2'] @entity263 :: ('MESH:D011471', 'Disease') :: ['Prostate cancer', 'PCa'] @entity6023 :: ('MESH:D043823', 'Chemical') :: ['taxanes'] @entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive tumors'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'tumor', 'cancer', 'tumors'] @entity1009 :: ('966', 'Gene') :: ['CD59'] @entity68829 :: ('8813', 'Gene') :: ['DPM1'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity60955 :: ('6137', 'Gene') :: ['RPL13'] @entity68827 :: ('5096', 'Gene') :: ['PCCB'] @entity30291 :: ('1031', 'Gene') :: ['CDKN2C'] @entity1178 :: ('3725', 'Gene') :: ['JUN'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity15513 :: ('MESH:C552428', 'Chemical') :: ['cabazitaxel'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel']
@entity901 :: (MESH:C030110,Chemical) :: ['oxaliplatin']
