Project description:Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq).
Project description:Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks
Project description:Docetaxel chemotherapy in metastatic prostate cancer offers only a modest survival benefit due to emerging resistance. To identify candidate therapeutic gene targets, we applied a murine prostate cancer orthograft model that recapitulates clinical invasive prostate cancer in a genome-wide CRISPR/Cas9 screen under docetaxel treatment pressure.
Project description:Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment. The aim of the study was to identify key molecular genes and networks associated with docetaxel resistance in 2 models of docetaxel-resistant castration-resistant prostate cancer cell lines.
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients 12 samples were analysed. A genome-wide expression array was performed on a GeneChip Human Gene 2.0ST Array (Affymetrix, 902112) with C4-2 cells, treated for 16h with 1nM cabazitaxel, docetaxel or vehicle (EtOH), in duplicates. The expression data were RMA normalized, and filtered to remove low-expressing genes. Differential gene expression with corresponding p-values (student’s ttest) was determined of drug-treated over control.
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients 12 samples were analysed. A genome-wide expression array was performed on a GeneChip Human Gene 2.0ST Array (Affymetrix, 902112) with LNCaP cells infected with a control plasmid (MSCV-LMP), treated for 16h with 1nM cabazitaxel, docetaxel or vehicle (EtOH), in duplicates. The expression data were RMA normalized, and filtered to remove low-expressing genes. Differential gene expression with corresponding p-values (student’s ttest) was determined of drug-treated over control.
Project description:Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment. The aim of the study was to identify key molecular genes and networks associated with docetaxel resistance in 2 models of docetaxel-resistant castration-resistant prostate cancer cell lines. DU-145 and PC-3 cells were converted to docetaxel-resistant cells, DU-145R and PC-3R, respectively. Whole-genome arrays were used to compare global gene expression between these 4 cell lines. Arrays were performed by triplicate for each cell line.