Neural invasion in pancreatic cancer: the past, present and future

In the past 15 years, invasion of nerves by cancer cells has escaped from its role as a mere bystander in cancer biology and turned into an attractive niche to study the heterotypic interaction between cancer cells and neurons. Today, neural invasion (NI) in pancreatic cancer (PCa) stands out due to the recent demonstration of its association with tumor progression, local recurrence and neuropathic pain. Accordingly, recent research on NI in PCa revealed the critical involvement of numerous nerve- or cancer cell-derived molecules in several novel in vitro and in vivo models of NI, which, however, still need further major improvement.