TRPV6-Mediated Ca2+ Signaling in Pancreatic Ductal Adenocarcinoma: From Cellular Physiology to Therapeutic Opportunities

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type in which therapeutic options are limited, and the disease is characterized by a poor prognosis. In the development of pancreatic cancer, dysregulated Ca2+ signaling plays a key role by regulating proliferation, survival, metabolic adaptation, and tumor–microenvironment interactions. Among the Ca2+ channels, TRPV6 has emerged as a key regulator since this channel is highly selective for Ca2+ and frequently overexpressed in different types of cancers. The aim of this review is to summarize our current knowledge on the structure, regulation, and function of TRPV6, with emphasis on its cell-type specific roles within the pancreas. We describe the mechanisms by which TRPV6-mediated Ca2+ influx activates oncogenic signaling pathways, such as NFAT, AKT/mTOR, and NF-κB, and how this channel plays a role in intra- and extracellular pH regulation. In addition, the clinical relevance and potential contribution of TRPV6 to therapy resistance are discussed. Finally, we review pharmacological strategies and future perspectives regarding TRPV6 in PDAC.