The Role of Trpv6 in Pancreatic Ductal Cells and Pancreatic Cancer: Expression, Mechanisms, and Therapeutic Perspectives

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 cancers, dysregulated calcium signaling plays a key role, due to the regulation of proliferation, survival, metabolic adaptation, and tumor–microenvironment interactions. Among the calcium channels, TRPV6 has emerged as a key regulator since this channel is highly selective for calcium and frequently overex-pressed in different types of cancers. The aim of this review is to summarize our cur-rent 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 calcium influx activates oncogenic signaling pathways, such as NFAT, AKT/mTOR, and NF-κB, and how this channel plays a role in intra- and extra-cellular pH regulation. In addition, the clinical relevance and potential contribution of TRPV6 to therapy resistance are discussed. Finally, we review pharmacological strate-gies and future perspectives regarding TRPV6 in PDAC.