Project description
Pancreatic cancer characterisation at the single-cell level
Pancreatic ductal adenocarcinoma (PDAC) remains a cancer with dismal prognosis. However, recent evidence indicates that stratification into different subtypes provides a better guide for treatment decision. Despite patient heterogeneity and a lack of robust data, certain transcription factors are believed to act as drivers for these subtypes, and changes in their expression may even facilitate subtype switching. The EU-funded PDASwITch project will explore the role of the tumour microenvironment in this phenomenon. Using powerful high throughput single-cell profiling technologies, scientists will characterise the dynamic crosstalk between cancer cells and how this affects their phenotype. The ultimate goal is to clinically convert non-responder to responder tumours and improve patient outcome.
Objective
"Recently discovered subtypes in pancreatic ductal adenocarcinoma (PDAC) have potential to better guide the choice of therapy. However, this is challenged by the lack of robust data, patient heterogeneity, tumour cell plasticity, dynamic crosstalk with surrounding cells, and post-chemotherapy induced alterations. A few transcription factors may act as drivers of specific PDAC subtypes and changes in there expression through aberrant activation of super-enhancers may lead to ‘’subtype switching’’. However, the effect of the tumour-microenvironment on enhancer-driven gene expression programme to promote ‘’subtype switching’’ in pancreatic tumour cells remains largely unexplored. Hence, with this proposal I aim to provide in-depth characterization of this dynamic crosstalk combining reporter tracing through fluorescent labelling of subtype-specific transcriptional drivers of tumour cell states with powerful high throughput single-cell technologies, and super-enhancer single cell profiling which will translate to a clinical study of neoadjuvant chemotherapy with sequential tumour sample profiling. This work will ultimately provide a platform for the development of methods to precisely determine the ""phenotypic"" state of PDAC cells and aid in designing new agents to target these processes, with the ultimate goal of converting non-responder to responder tumours and improve patient outcome."
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
28029 Madrid
Spain