Work

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

Year: 2026

Type: article

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.

Source: Cells

DOI: 10.3390/cells15201857

Authors: Xinxing Cui, Yun He, Liu Yang, Aiping Lu, Fangfei Li

Institution: Hong Kong Baptist University

Language: English

Topic: Cancer, Stress, Anesthesia, and Immune Response

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258