Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease of the exocrine pancreas with poor prognosis. Its abundant stroma is largely composed of activated pancreatic stellate cells, responsible for the synthesis of great amounts of extracellular matrix (ECM) proteins. The high deposition of ECM components causes an increase in tissue rigidity and interstitial fluid pressure (from ~1 kPa in healthy tissue to ~10-17 kPa in tumoral tissue), while reducing tissue permeability. Thus, treating the PDAC with conventional approaches like chemotherapy and immunotherapy gives poor results. Cancer and stroma cells sense the mechanical cues of the tumor environment through mechanosensitive membrane proteins, prominently ion channels involved in the Ca2+-signaling of cells, and their crucial role in integrating signals makes them good therapeutic target candidates.