Ca2+ Signaling and Its Potential Targeting in Pancreatic Ductal Carcinoma

Simple Summary Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death in the world and is estimated to be the second cause of cancer deaths by 2030. Its complicity of treatment is explained by unique physiology and microenvironment of the exocrine pancreas, where calcium plays an essential role. This review is focused on the Ca2+-dependent proteins and signalization pathways studied so far in pancreatic adenocarcinoma. Ca2+ signaling is suggested as potential and prospective target in pancreatic carcinoma treatment and drug resistance. Pancreatic cancer (PC) is a major cause of cancer-associated mortality in Western countries (and estimated to be the second cause of cancer deaths by 2030). The main form of PC is pancreatic adenocarcinoma, which is the fourth most common cause of cancer-related death, and this situation has remained virtually unchanged for several decades. Pancreatic ductal adenocarcinoma (PDAC) is inherently linked to the unique physiology and microenvironment of the exocrine pancreas, such as pH, mechanical stress, and hypoxia. Of them, calcium (Ca2+) signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer. Mutations or aberrant expression of key proteins that control Ca2+ levels can cause deregulation of Ca2+-dependent effectors that control signaling pathways determining the cells' behavior in a way that promotes pathophysiological cancer hallmarks, such as enhanced proliferation, survival and invasion. So far, it is essentially unknown how the cancer-associated Ca2+ signaling is regulated within the characteristic landscape of PDAC. This work provides a complete overview of the Ca2+ signaling and its main players in PDAC. Special consideration is given to the Ca2+ signaling as a potential target in PDAC treatment and its role in drug resistance.

Automated summary

Pancreatic adenocarcinoma is a major cause of cancer-related mortality, with Ca2+ signaling playing a crucial role in controlling signaling pathways that promote cancer hallmarks. Understanding and targeting Ca2+ signaling in pancreatic cancer treatment may be a key strategy in overcoming drug resistance and improving outcomes.