Inflammation is one of the major risk factors for pancreatic ductal adenocarcinoma, a tumor characterized by a very poor prognosis and projected to become the second leading cause of cancer death in United States in the next decade. As for other tumors, also in pancreatic cancer inflammation leads to accelerated tumor development promoting tumor growth through the activation of survival and proliferation programs in cancer cells. Recently, investigating the effects of inflammation on normal pancreatic epithelial cells we discovered that, even long after the complete resolution, transient inflammatory events prime epithelial cells to cooperate with mutated genes that drive tumors development....

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Inflammation is one of the major risk factors for pancreatic ductal adenocarcinoma, a tumor characterized by a very poor prognosis and projected to become the second leading cause of cancer death in United States in the next decade. As for other tumors, also in pancreatic cancer inflammation leads to accelerated tumor development promoting tumor growth through the activation of survival and proliferation programs in cancer cells. Recently, investigating the effects of inflammation on normal pancreatic epithelial cells we discovered that, even long after the complete resolution, transient inflammatory events prime epithelial cells to cooperate with mutated genes that drive tumors development. Indeed, after fully recovery, normal epithelial cells seem to acquire a ‘memory’ of previous inflammatory events and are more prone to become cancerous even in the absence of an ongoing inflammatory process. In this proposal, to better understand the molecular mechanisms underlying this interesting behavior, we will investigate the molecular mechanisms underpinning the epithelial memory and identify the mediators responsible for its acquisition. We will also investigate the relevance epithelial memory has for the maintenance of the integrity of the normal pancreatic tissue during physiologic conditions and regeneration in response to damage. We are confident this study is highly significant since intended to identify more effective therapeutic approaches able to resolve pancreatitis preventing the development of pancreatic cancer, a tumor characterized by a silent onset and very poor prognosis.

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