Nerves and pancreatic cancer: New insights into a dangerous relationship

Giulia Gasparini, Marta Pellegatta, Stefano Crippa, Marco Schiavo Lena, Giulio Belfiori, Claudio Doglioni, Carla Taveggia, Massimo Falconi

Research output: Contribution to journalReview articlepeer-review


Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: Epineural, perineural and endoneural spaces. In pancreatic cancer—particularly in pancreatic ductal adenocarcinoma (PDAC)—PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival. Such an early, invasive and recurrent phenomenon is probably crucial for tumor growth and metastasis. PNI is a still not a uniformly characterized event; usually it is described only dichotomously (“present” or “absent”). Recently, a more detailed scoring system for PNI has been proposed, though not specific for pancreatic cancer. Previous studies have implicated several molecules and pathways in PNI, among which are secreted neurotrophins, chemokines and inflammatory cells. However, the mechanisms underlying PNI are poorly understood and several aspects are actively being investigated. In this review, we will discuss the main molecules and signaling pathways implicated in PNI and their roles in the PDAC.

Original languageEnglish
Article number893
Issue number7
Publication statusPublished - Jul 2019


  • Molecular signaling
  • Neurotrophins
  • Pancreatic cancer
  • Perineural invasion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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