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Peer-reviewedCC BY 4.0Cells

Cancer-Associated Fibroblasts in Perineural Invasion: Biological Roles and Therapeutic Strategies

  • Xinxing Cui1,2,3
  • Yun He1,2,3
  • Liu Yang1,2,3
  • Aiping Lu1,2,3
  • Fangfei Li1,2,3
  1. 1Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research (CCIR), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
  2. 2Institute of Precision Medicine and Innovative Drug Discovery (PMID), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
  3. 3Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
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Abstract

Perineural invasion (PNI), the process of tumor cell infiltration of nerves, is a pathological feature of aggressive tumor behavior, correlating with therapeutic resistance and poor clinical outcomes. Cancer-associated fibroblasts (CAFs) have recently emerged as key regulators of PNI. CAFs drive PNI progression through multifaceted mechanisms, including dynamic remodeling of CAF subtypes, neural microenvironment remodeling, and enhancement of tumor–nerve crosstalk via neurotrophic signaling. While various therapeutic approaches targeting CAF surface markers, secreted factors, and intracellular signaling pathways are under investigation, none have yet been translated into clinical practice for PNI management. This review synthesizes current understanding of CAF-mediated PNI, highlights critical knowledge gaps, and proposes future directions. Here, we conceptualize CAF-mediated PNI as a coordinated process linking CAF subtype dynamics, neural niche remodeling, and tumor–nerve crosstalk, rather than as a collection of isolated pro-invasive mechanisms.

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Cite

BibTeXRIS
BibTeX
@article{cui2026cancerassociated,
  title = {{Cancer-Associated Fibroblasts in Perineural Invasion: Biological Roles and Therapeutic Strategies}},
  author = {Xinxing Cui and Yun He and Liu Yang and Aiping Lu and Fangfei Li},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15201857},
  url = {https://www.mdpi.com/2073-4409/15/20/1857},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cancer-Associated Fibroblasts in Perineural Invasion: Biological Roles and Therapeutic Strategies
AU  - Xinxing Cui
AU  - Yun He
AU  - Liu Yang
AU  - Aiping Lu
AU  - Fangfei Li
PY  - 2026
DA  - 2026/10/13
JO  - Cells
DO  - 10.3390/cells15201857
UR  - https://www.mdpi.com/2073-4409/15/20/1857
AB  - Perineural invasion (PNI), the process of tumor cell infiltration of nerves, is a pathological feature of aggressive tumor behavior, correlating with therapeutic resistance and poor clinical outcomes. Cancer-associated fibroblasts (CAFs) have recently emerged as key regulators of PNI. CAFs drive PNI progression through multifaceted mechanisms, including dynamic remodeling of CAF subtypes, neural microenvironment remodeling, and enhancement of tumor–nerve crosstalk via neurotrophic signaling. While various therapeutic approaches targeting CAF surface markers, secreted factors, and intracellular signaling pathways are under investigation, none have yet been translated into clinical practice for PNI management. This review synthesizes current understanding of CAF-mediated PNI, highlights critical knowledge gaps, and proposes future directions. Here, we conceptualize CAF-mediated PNI as a coordinated process linking CAF subtype dynamics, neural niche remodeling, and tumor–nerve crosstalk, rather than as a collection of isolated pro-invasive mechanisms.
SN  - 2073-4409
ER  -