Microenvironnement and Therapeutic Resistance
in Pancreatic Neoplasms
OF OUR RESEARCH AXIS
Pancreatic ductal adenocarcinoma (PDAC), commonly known as pancreatic cancer, is a very aggressive tumor since it presents a rapid metastatic potential and a strong therapeutic resistance. This tumor has the particularity of being rich in stroma (up to 80% of its tumor volume), composed of a very fibrotic extracellular matrix, and of immune and non-immune stromal cells, of which cancer-associated fibroblasts (CAFs) are the majority. My research team is specifically interested in the role of CAFs in the aggressiveness of pancreatic cancer cells, with the objective of understanding the biology of CAFs, their dialogues with cancer cells and with other stromal cells (endothelial and immune), and how these dialogues impact the resistance of cancer cells to chemotherapies or immunotherapies. The understanding of these inter-cellular dialogues and with the extracellular matrix allows us to propose and test anti-cancer therapies co-targeting cancer cells and their stroma, in particular by targeted nanotherapies approaches (Veronique Gigoux’s project).
Thus, to understand the tumor-stroma dialogues correlated with the aggressiveness of pancreatic cancer, our team is i/ developing models integrating this stroma and mimicking the pathology in the patient, such as PDX (Patient-Derived Xenografts) and primocultures of CAFs and tumor cells grown in 3 dimensions (tumor organoids) and in co-culture with CAFs, as well as murine pancreatic cancer models (genetically modified mice developing spontaneous cancer, and orthotopic surgical transplantation of pancreatic cancer cells with CAFs) ; and ii/ perform
s separate analyses of gene expression in the tumor epithelial compartment and in the stromal compartment, using transcriptomics (mRNA expression), transla ctomics (translated RNA expression, project of Yvan Martineau), and matrisome (exhaustive analysis of matrix proteins expression, Christine Jean’s project) on PDX (hybrid grafted tumor models) naïve to treatment or rendered chemoresistant (Corinne Bousquet’s project), and/or by bioinformatics deconvolution on bulk RNAseq of human tumors
Tumor organoid (left: immunofluorescence to visualize the cytokeratin cytoskeleton in green, the actin filaments particularly abundant at the brush border in pink and the nuclei in blue; right: transmission electron microscopy).
Microenvironment & Cancer-Associated Fibroblasts
Matrix rigidity & mechano-transduction
Patient-derived experimental models
(polysome) RNAseq & bioinformatics
Multiplexed tissue imaging
Identification of tumor-stroma dialogues involved in the aggressiveness of pancreatic cancer
Targeted nanotherapies applied to pancreatic adenocarcinoma
Role of fibroblastic focal adhesion kinase (fak) in pancreatic adenocarcinoma
Mrna translation analysis as a new approach to classify pancreatic tumors
parternships & FUNDING
Centre de Recherches en Cancérologie de Toulouse (Oncopole)
Toulouse – FR
05 82 74 15 75
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