Pancreatic Cancer-Secreted Proteins: Targeting Their Functions in Tumor Microenvironment

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related deaths by 2030. The main reasons for such a poor prognosis can be attributed to the particularly complex anatomical region in which the tumor grows, as well as the fact that this tumor is usually diagnosed at an advanced stage in most patients. At the molecular level, heterogeneous oncogenic and loss-of-function mutations in tumor suppressors, in which KRAS variants are the most frequent, characterize pancreatic cancer cells. Furthermore, altered ductal cells constitute only a modest portion of pancreatic cancer tumor mass, with the remainder made up of stromal cells and components. Indeed, the complex tumor microenvironment (TME) and communication between tumor and stromal cells are associated with different tumor cell phenotypes. In this context, transformed cells are the source of different extracellular signals that, when captured by nearby non-transformed stromal cells, influence tumor formation, metastasis, and even treatment efficacy. In this context, it is evident that this disease urgently requires a better knowledge of its biology in order to develop effective treatments. Here, we draw a special attention to pancreatic cancer-secreted proteins, which are primary players in the development and the maintenance of the “cancer-friendly” environment and reported, in this framework, druggable molecular targets for the design of more effective therapeutic treatments. ABSTRACT: Pancreatic Ductal Adenocarcinoma (PDAC) is a ravaging disease with a poor prognosis, requiring a more detailed understanding of its biology to foster the development of effective therapies. The unsatisfactory results of treatments targeting cell proliferation and its related mechanisms suggest a shift in focus towards the inflammatory tumor microenvironment (TME). Here, we discuss the role of cancer-secreted proteins in the complex TME tumor-stroma crosstalk, shedding lights on druggable molecular targets for the development of innovative, safer and more efficient therapeutic strategies.