Neural Remodeling Across Cancer Evolution: Temporal, Spatial, Cellular, and Functional Principles of Tumor–Nerve Ecosystems
- 1Oncologic Pathology Department, National Cancer Institute, Cairo University, Giza P.O. Box 12613, Egypt
- 2Department of Community Medicine, College of Medicine, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates
- 3Chemistry Department, Faculty of Science, Cairo University, Giza P.O. Box 12613, Egypt
Abstract
Cancer neuroscience now asks not only whether tumors contain nerves, but how neural architecture, neuronal and glial states, and neural output change through cancer evolution. This critical narrative review integrates evidence from precursor lesions, primary tumors, invasion, metastasis, and treatment-associated states, while distinguishing neural remodeling from axonogenesis, neurogenesis, perineural invasion, and direct synaptic integration. We compare trophic, axon-guidance, metabolic, extracellular-vesicle, stromal, and neuroimmune mechanisms and emphasize that the direction of neural effects depends on stage, neuronal subtype, receptor context, and tissue immunity. The review operationalizes the proposed neural microdomain as a spatially bounded, measurable unit linking neural identity and topology to neighboring tumor, immune, stromal, and vascular states. It also separates neural abundance, neural state, and neural activity, and applies a consistent evidence taxonomy spanning anatomical, molecular, preclinical functional, human observational, and interventional evidence. Recent reports involving treatment-associated remodeling, systemic circuits, metastatic adaptation, and neural biomarkers are treated as emerging or preclinical where appropriate. We provide practical criteria for microdomain measurement, patient-level quantitative analysis, controls for denervation-related confounding, and distinctions among prognostic, predictive, and response biomarkers. The central translational conclusion is that neural interventions should be stage- and circuit-specific, biomarker-supported, and designed to preserve essential physiological neural functions.
Related
- Pathological remodeling and functional evolution of the corneal nervous system in ocular surface dyshomeostasis.
- Single-cell and spatial transcriptomics in intrahepatic cholangiocarcinoma: spatial immune ecosystems, metabolic remodeling, and immunotherapeutic implications
- Evolution of fertility-related genes provides insights into morphological remodeling and enhanced thermal stability of sperm in naturally cryptorchid mammals
- Beyond Remodeling: Four Structural–Functional Recovery Patterns as a Framework for Interpreting Ventricular Recovery After Reperfused STEMI
- Temporal N-terminomics analysis reveals proteome remodeling following brensocatib-mediated cathepsin C inhibition in promyeloblast cells
BibTeX
@article{ebrahim2026neural,
title = {{Neural Remodeling Across Cancer Evolution: Temporal, Spatial, Cellular, and Functional Principles of Tumor–Nerve Ecosystems}},
author = {Noura A. A. Ebrahim and Rasha Aziz Attia Salama and Soliman M. A. Soliman},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213504},
url = {https://www.mdpi.com/2072-6694/18/21/3504},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neural Remodeling Across Cancer Evolution: Temporal, Spatial, Cellular, and Functional Principles of Tumor–Nerve Ecosystems
AU - Noura A. A. Ebrahim
AU - Rasha Aziz Attia Salama
AU - Soliman M. A. Soliman
PY - 2026
DA - 2026/10/30
JO - Cancers
DO - 10.3390/cancers18213504
UR - https://www.mdpi.com/2072-6694/18/21/3504
AB - Cancer neuroscience now asks not only whether tumors contain nerves, but how neural architecture, neuronal and glial states, and neural output change through cancer evolution. This critical narrative review integrates evidence from precursor lesions, primary tumors, invasion, metastasis, and treatment-associated states, while distinguishing neural remodeling from axonogenesis, neurogenesis, perineural invasion, and direct synaptic integration. We compare trophic, axon-guidance, metabolic, extracellular-vesicle, stromal, and neuroimmune mechanisms and emphasize that the direction of neural effects depends on stage, neuronal subtype, receptor context, and tissue immunity. The review operationalizes the proposed neural microdomain as a spatially bounded, measurable unit linking neural identity and topology to neighboring tumor, immune, stromal, and vascular states. It also separates neural abundance, neural state, and neural activity, and applies a consistent evidence taxonomy spanning anatomical, molecular, preclinical functional, human observational, and interventional evidence. Recent reports involving treatment-associated remodeling, systemic circuits, metastatic adaptation, and neural biomarkers are treated as emerging or preclinical where appropriate. We provide practical criteria for microdomain measurement, patient-level quantitative analysis, controls for denervation-related confounding, and distinctions among prognostic, predictive, and response biomarkers. The central translational conclusion is that neural interventions should be stage- and circuit-specific, biomarker-supported, and designed to preserve essential physiological neural functions.
SN - 2072-6694
ER -