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REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1572396
Significance and mechanisms of perineural invasion in malignant tumors
Provisionally accepted- Affiliated Tumor Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, China
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Cancer remains the second leading cause of death worldwide. Tumor invasion and metastasis pose significant challenges for clinical management. In addition to the traditional pathways of metastasis such as hematologic or lymphatic transmission, perineural invasion (PNI) has become a unique mechanism of metastasis, which is closely associated with neuropathic pain, motor deficits, and poor prognosis. PNI is often observed in malignant tumors of the pancreas, head and neck, gastrointestinal tract, and lungs, and it reflects a unique neurotropic transfer behavior utilizing neural networks. Despite its clinical significance, targeted therapies for PNI are still lacking. This review synthesizes current evidences regarding PNI, elucidates the clinical significance of PNI in tumor metastasis, prognosis, and neurological dysfunction. By integrating the latest advances in multi-omics, we analyzed the potential key molecular pathways and tumor microenvironment drivers of PNI, and proposed future research directions for developing PNI-specific therapies to improve patient outcomes.
Keywords: Malignant tumors, Perineural invasion, Molecular mechanisms, Tumor Microenvironment, perineural invasion models ERK, extracellular signal-regulated kinases, bFGF, basic fibroblast growth factor, DRGs, dorsal root ganglia, PSCs, pancreatic stellate cells
Received: 07 Feb 2025; Accepted: 18 Apr 2025.
Copyright: © 2025 Wang, Pu, Bo, Chen, Zhou and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qiong Cheng, Affiliated Tumor Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.