New insights into perineural invasion of pancreatic cancer: More than pain

Pancreatic cancer is one of the most malignant human tumors. Perineural invasion, whereby a cancer cell invades the perineural spaces surrounding nerves, is acknowledged as a gradual contributor to cancer aggressiveness. Furthermore, perineural invasion is considered one of the root causes of the recurrence and metastasis observed after pancreatic resection, and it is also an independent predictor of prognosis. Advanced research has demonstrated that the neural microenvironment is closely associated with perineural invasion in pancreatic cancer. Therapy targeting the molecular mechanism of perineural invasion may enable the durable clinical treatment of this formidable disease. This review provides an overview of the present status of perineural invasion, the relevant molecular mechanisms of perineural invasion, pain and hyperglycemia associated with perineural invasion in pancreatic cancer, and the targeted therapeutics based on these studies. (C) 2016 Elsevier B.V. All rights reserved.