Coexisting morpho-biotypes unveil the regulatory bases of phenotypic plasticity in pancreatic ductal adenocarcinoma

Coexisting morpho-biotypes unveil the regulatory bases of phenotypic plasticity in pancreatic ductal adenocarcinoma
Prof. Luigi Di Chiaro - Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with an extremely aggressive behavior. The lack of effective treatment approaches may be due to the presence of an extensive cellular and architectural heterogeneity described in the majority of PDAC cases. However, this cellular variability is only partially understood at the molecular level reflecting a significant knowledge gap between intra-tumor morphological variation and molecular understanding of PDAC heterogeneity.
In this study, we set out to determine the gene regulatory networks and expression programs supporting the intratumor morphological heterogeneity in PDAC.
We used laser micro-dissection (LMD) and single cell approaches to identify three main morpho-biotypes, defined as spatially organized groups of single tumors cells with distinct morphological patterns, molecular profiles and clinical properties, that coexist in various proportions in individual tumors.
The identification of PDAC morpho-biotypes may help to improve patient stratification and therapeutic schemes with direct implications for target-specific combinatorial therapies.

AUTHORS:

Pierluigi Di Chiaro, Lucia Nacci, Stefania Brandini, Giuseppe Riccardo Diaferia, Gioacchino Natoli.

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