Matches in SemOpenAlex for { <https://semopenalex.org/work/W2230447234> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2230447234 endingPage "e14087" @default.
- W2230447234 startingPage "e14087" @default.
- W2230447234 abstract "e14087 Background: The discovery of underlying mechanisms of drug resistance and the development of novel agents to target these pathways is a priority for patients with advanced colorectal cancer (CRC). The fibroblast growth factor receptor 4 (FGFR4) is frequently overexpressed in solid tumours, such as CRC, and has been shown to be an important regulator of cancer cell growth and motility. The aim of this study was to identify novel targets whose knock-down is important in mediating sensitivity to 5-FU and oxaliplatin in Kras wild-type (WT) and mutant (MT) CRC models. Methods: Transcriptional profiling (Almac Diagnostics CRC Disease Specific Array) of pre-treatment metastatic CRC liver biopsies and oxaliplatin/5-FU resistant HCT116 cell lines followed by Metacoreä and Gene Set Enrichment Analysis (GSEA) were used to identify individual genes from novel drug-sensitivity pathways for incorporation into a RNAi screen. Results: We identified panels of in vitro and clinical genes whose expression is altered (acutely and basally) between sensitive and 5-FU- or oxaliplatin-resistant models. The significant pathways involved in 5-FU/oxaliplatin resistance included cell cycle, focal adhesion, insulin and MAPK signalling. In the MAPK pathway, we found that FGFR4 silencing potently increased apoptosis in KrasWT and MT CRC cells, and this was further enhanced when FGFR4 siRNA was combined with 5-FU or oxaliplatin. Interestingly, FGFR4 inhibition completely inhibited migration of KrasMT HCT116 cells. Mechanistically, we found that FGFR4, silencing resulted in strong inhibition of STAT3 activity in both KrasWT and MT CRC cells. Conclusions: This study demonstrates the utility of microarray expression data, obtained from pre-clinical and clinical samples, and analyzed by pathway and gene set enrichment analysis to identify pathways of oxaliplatin/5-FU sensitivity in CRC. In addition FGFR4 inhibition in combination with 5-FU or oxaliplatin could represent a novel treatment strategy for KrasMT and WT CRC tumours. We are currently investigating FGFR4 small molecule inhibitors in preclinical in vitro and in vivo models." @default.
- W2230447234 created "2016-06-24" @default.
- W2230447234 creator A5001477380 @default.
- W2230447234 creator A5005391044 @default.
- W2230447234 creator A5016266460 @default.
- W2230447234 creator A5017147519 @default.
- W2230447234 creator A5027083485 @default.
- W2230447234 creator A5031840599 @default.
- W2230447234 creator A5041076326 @default.
- W2230447234 creator A5046007476 @default.
- W2230447234 creator A5064190261 @default.
- W2230447234 creator A5065989372 @default.
- W2230447234 creator A5078841356 @default.
- W2230447234 date "2011-05-20" @default.
- W2230447234 modified "2023-09-23" @default.
- W2230447234 title "Inhibition of FGFR4 increases oxaliplatin and 5-fluorouracil sensitivity in Kras wild-type and mutant colorectal cancer cells." @default.
- W2230447234 doi "https://doi.org/10.1200/jco.2011.29.15_suppl.e14087" @default.
- W2230447234 hasPublicationYear "2011" @default.
- W2230447234 type Work @default.
- W2230447234 sameAs 2230447234 @default.
- W2230447234 citedByCount "0" @default.
- W2230447234 crossrefType "journal-article" @default.
- W2230447234 hasAuthorship W2230447234A5001477380 @default.
- W2230447234 hasAuthorship W2230447234A5005391044 @default.
- W2230447234 hasAuthorship W2230447234A5016266460 @default.
- W2230447234 hasAuthorship W2230447234A5017147519 @default.
- W2230447234 hasAuthorship W2230447234A5027083485 @default.
- W2230447234 hasAuthorship W2230447234A5031840599 @default.
- W2230447234 hasAuthorship W2230447234A5041076326 @default.
- W2230447234 hasAuthorship W2230447234A5046007476 @default.
- W2230447234 hasAuthorship W2230447234A5064190261 @default.
- W2230447234 hasAuthorship W2230447234A5065989372 @default.
- W2230447234 hasAuthorship W2230447234A5078841356 @default.
- W2230447234 hasConcept C104317684 @default.
- W2230447234 hasConcept C119056186 @default.
- W2230447234 hasConcept C121608353 @default.
- W2230447234 hasConcept C126322002 @default.
- W2230447234 hasConcept C2779998722 @default.
- W2230447234 hasConcept C2780962732 @default.
- W2230447234 hasConcept C2781187634 @default.
- W2230447234 hasConcept C502942594 @default.
- W2230447234 hasConcept C526805850 @default.
- W2230447234 hasConcept C54355233 @default.
- W2230447234 hasConcept C57074206 @default.
- W2230447234 hasConcept C62478195 @default.
- W2230447234 hasConcept C71924100 @default.
- W2230447234 hasConcept C86803240 @default.
- W2230447234 hasConcept C95444343 @default.
- W2230447234 hasConceptScore W2230447234C104317684 @default.
- W2230447234 hasConceptScore W2230447234C119056186 @default.
- W2230447234 hasConceptScore W2230447234C121608353 @default.
- W2230447234 hasConceptScore W2230447234C126322002 @default.
- W2230447234 hasConceptScore W2230447234C2779998722 @default.
- W2230447234 hasConceptScore W2230447234C2780962732 @default.
- W2230447234 hasConceptScore W2230447234C2781187634 @default.
- W2230447234 hasConceptScore W2230447234C502942594 @default.
- W2230447234 hasConceptScore W2230447234C526805850 @default.
- W2230447234 hasConceptScore W2230447234C54355233 @default.
- W2230447234 hasConceptScore W2230447234C57074206 @default.
- W2230447234 hasConceptScore W2230447234C62478195 @default.
- W2230447234 hasConceptScore W2230447234C71924100 @default.
- W2230447234 hasConceptScore W2230447234C86803240 @default.
- W2230447234 hasConceptScore W2230447234C95444343 @default.
- W2230447234 hasIssue "15_suppl" @default.
- W2230447234 hasLocation W22304472341 @default.
- W2230447234 hasOpenAccess W2230447234 @default.
- W2230447234 hasPrimaryLocation W22304472341 @default.
- W2230447234 hasRelatedWork W1980946342 @default.
- W2230447234 hasRelatedWork W2010163599 @default.
- W2230447234 hasRelatedWork W2022483081 @default.
- W2230447234 hasRelatedWork W2048054271 @default.
- W2230447234 hasRelatedWork W2055209074 @default.
- W2230447234 hasRelatedWork W2382373186 @default.
- W2230447234 hasRelatedWork W2941329250 @default.
- W2230447234 hasRelatedWork W2944268665 @default.
- W2230447234 hasRelatedWork W3002562664 @default.
- W2230447234 hasRelatedWork W2188887532 @default.
- W2230447234 hasVolume "29" @default.
- W2230447234 isParatext "false" @default.
- W2230447234 isRetracted "false" @default.
- W2230447234 magId "2230447234" @default.
- W2230447234 workType "article" @default.