Cancer neuroscience: Mechanistic advances in neural infiltration, circuit remodeling, and tumor microenvironment modulation
1 Department of Medical Laboratory Science, Lead City University, Ibadan, Nigeria.
2 Department of Biotechnology, University of Texas Health Sciences Center at Tyler, USA.
3 Department of Biochemistry, Federal University of Technology, Minna, Nigeria.
4 Department of Human Physiology, Federal University Lokoja, Nigeria.
5 Department of College of Medicine, Lagos State University, Ojo, Lagos, Nigeria.
6 Department of Histopathology, National Hospital Abuja, Nigeria.
7 Department of Internal Medicine (Consulting group), Obafemi Awolowo University Health center, Ile-Ife, Osun, Nigeria.
Review
International Journal of Biological and Pharmaceutical Sciences Archive, 2025, 10(01), 141-172.
Article DOI: 10.53771/ijbpsa.2025.10.1.0062
Publication history:
Received on 16 July 2025; revised on 24 August 2025; accepted on 26 August 2025
Abstract:
The intricate interplay between tumors and the nervous system has emerged as a transformative frontier in oncology, redefining our understanding of cancer progression and unveiling novel therapeutic horizons. This review synthesizes cutting-edge advances in cancer neuroscience, illuminating how tumor–neuron interactions drive malignancy across cancers such as glioblastoma, pancreatic ductal adenocarcinoma, prostate, and breast cancer. Tumors actively recruit peripheral and autonomic nerves through neurotrophic signaling, fostering perineural invasion and establishing feedback loops that amplify tumor growth and metastasis. Gliomas, in particular, form synapse-like structures with neurons, harnessing glutamatergic signaling to enhance proliferation and invasion, while neural modulation of the immune microenvironment promotes immunosuppression, shielding tumors from immune surveillance. Neural signaling further sustains cancer stem cell niches, fueling tumor dormancy and recurrence. Innovative therapeutic strategies, including surgical denervation, pharmacological inhibitors like β-blockers and AMPA receptor antagonists, and CRISPR-based gene silencing, show promise in disrupting these neural-driven mechanisms, with combination therapies enhancing the efficacy of immunotherapy and chemotherapy. Advanced tools, such as spatial transcriptomics, single-cell RNA sequencing, optogenetics, and electrophysiology, have unraveled the molecular and functional dynamics of tumor–neuron crosstalk, paving the way for precision oncology. Despite these breakthroughs, challenges like tumor heterogeneity, neurotoxicity, and technological barriers underscore the need for targeted delivery systems and robust clinical trials. By bridging neuroscience and oncology, this review highlights the transformative potential of targeting tumor–neuron interactions to improve patient outcomes, offering a compelling vision for future research and clinical innovation in the fight against neurologically active cancers.
Keywords:
Cancer Neuroscience; Tumor–Neuron Interactions; Perineural Invasion; Glutamatergic Signaling; Neural Circuit Remodeling; Immunosuppression; Cancer Stem Cells; Synaptic Therapies
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Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0