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Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant stromal response also known as a desmoplastic reaction. Pancreatic Stellate Cells have been identified as playing a key role in pancreatic cancer desmoplasia. There is accumulating evidence that the stroma contributes to tumour progression and to the low therapeutic response of PDAC patients. In this review we described the main actors of the desmoplastic reaction within PDAC and novel therapeutic approaches that are being tested to block the detrimental function of the stroma.