Profiling cellular heterogeneity of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. In most cases it is only diagnosed at late stages, although there is much evidence supporting the idea that progression from pre-invasive lesions to cancer is slow. Understanding the early events that initiate the hazardous processes that eventually lead to PDAC will assist in finding biomarkers to improve early diagnosis. It will also shed light on the interactions between the stroma and the malignant cells that support the development of the disease and therefore will offer new therapeutic targets. We use high-throughput genomic methods to profile cellular heterogeneity in mice models of pre-malignant stage and of advanced tumor and in human PDAC samples. Our data reveal unexpected heterogeneity in epithelial cell identities showing metaplasia to different lineages at the pre-invasive stage. We are currently exploring whether this process is protective or pro-tumorigenic. In addition, our data suggest new mechanisms of involvement of stroma cells in supporting the development of the disease and the formation of an immunosuppressive environment at early stages of pre-malignant lesions. Furthermore, we are currently developing genetic methods and a novel in vitro system to validate the main findings of the genomic analysis. We expect that our high throughput genomic and genetic efforts will reveal complicated processes that give rise to PDAC and will assist in finding new biomarkers and clinically relevant targets.