The role of non-cancerous cells in cancer: Pancreatic ductal adenocarcinoma as a model to understand the impact of tumor microenvironment on epithelial carcinogenesis

Pancreatic ductal adenocarcinoma is a deadly tumor. Despite several advances in conventional and targeted therapies over decades, its mortality remains slightly less than its frequency. One of its main features is its compact stroma which is formed by pancreatic stellate cells. In the last decade, it became evident that the stromal component of the tumor is not a passive scaffold, but an active player in carcinogenesis. This component is mostly missing in our experimental settings. Even in genetically engineered mouse models where a fibrotic stroma is visible, tumor responses are different than in humans. Our inability to recreate the tumor microenvironment often leads to optimistic results in the therapy of pancreatic cancer. This temporary optimism is often lost after first clinical trials. Here we would summarize various approaches to treat pancreatic cancer and scrutinize their pros and cons from a biologic point of view.