Discovery of Novel Targets in Pancreatic Cancer by Investigating Aberrant Signalling Pathways
Prof Geoffrey Candy
Title of the project
Discovery of novel targets in pancreatic cancer by investigating aberrant signalling pathways.
Pancreatic cancer (PDAC) is a devastating and aggressive cancer with a poor prognosis despite several treatment strategies. Hence the discovery of potential new therapeutic targets is essential to improve outcomes. Dysregulation of several key pathways occur during PDAC. Previous study in our laboratory has identified several of these pathways (Nweke et al, submitted for publication). This approach identified alterations in pathways including IGF/MAPK, Ras, EGFR, integrin, PDGF, CCKR and VEGF. These pathways have been identified to be involved in cellular proliferation, invasion and migration. The current study uniquely utilizes pathway-based approach to identify potential therapeutic targets and intends to investigate the functions of these targets.
To identify (novel) gene targets in dysregulated pathways implicated in the progression of PDAC.
Tissue samples would be collected from consenting patients at the Hepatobiliary Units at the Chris Hani Baragwaneth and Charlotte Maxeke Hospitals Johannesburg. Total RNA would be extracted and a nCounter PanCancer pathway panel used for gene expression analysis. This will help identify target genes that may be involved in PDAC initiation and progression. Real-time PCR would be used for the validation of identified gene targets. Gene targets would also be knocked down in cell lines and cell viability assays performed using flow cytometry. Analysis of data obtained would use the nSolver™ analysis, GenEx and FloJo software for the nCounter, real-time PCR and flow cytometry-based assays.
The study would identify (novel) gene targets in various dysregulated pathways that could be used for future effective therapies.