Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer

Pancreatic cancer is a major cause of demise worldwide. Although key associ-ated genetic changes have been discovered, disease progression is sustained by pathogenic mechanisms that are poorly understood at the molecular level. In particular, the tissue microenvironment of pancreatic adenocarcinoma (PDAC) is usually characterized by high stromal content, scarce recruitment of immune cells, and the presence of neuronal fibers. Semaphorins and their recep-tors, plexins and neuropilins, comprise a wide family of regulatory signals that control neurons, endothelial and immune cells, embryo development, and nor-mal tissue homeostasis, as well as the microenvironment of human tumors. We focus on the role of these molecular signals in pancreatic cancer progression, as revealed by experimental research and clinical studies, including novel ap-proaches for cancer treatment.

Automated summary

This article discusses the role of Semaphorins and their receptors, Plexin and Neuropilin, in the progression of pancreatic cancer. These signaling molecules regulate neurons, endothelial cells, immune cells, and the microenvironment of tumors.