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Cancer Neuroscience: Unveiling the Intricate Interplay between Nervous System and Cancer

Cancer neuroscience emerges as a promising field, delving into the intricate connections between the nervous system and cancer. This multifaceted relationship unveils its impact on tumor initiation, progression, and metastasis. By comprehensively reviewing key concepts in cancer neuroscience, this article elucidates the bidirectional communication between the nervous system and tumors, offering potential therapeutic strategies and a deeper comprehension of cancer progression.


The intricate interplay between the nervous system and cancer becomes evident when considering the role of neurons in tumor growth and invasion, as well as the reciprocal influence of tumors on neural function. Gliomas, the most common primary brain cancers, establish synaptic connections with neurons, promoting tumor growth and invasion.[1] Remarkably, neural activity can either enhance or inhibit glioma growth, revealing the complex interplay between the nervous system and cancer biology.


Moreover, the tumor microenvironment, composed of cancer cells, stromal cells, immune cells, and blood vessels, plays a pivotal role in tumor growth and therapeutic responses. The sympathetic nervous system (SNS) significantly contributes to this microenvironment, impacting angiogenesis and immune modulation within tumors.[1] This highlights the intricate interplay between neural signalling and tumor behavior within the complex milieu of the tumor microenvironment.


Figure 1. Mechanisms of nervous system-cancer interactions. Image is adapted from [4]


Metastasis, a critical determinant of patient prognosis, involves the spread of cancer cells to distant organs. Epithelial-mesenchymal transition (EMT) empowers cancer cells with the ability to migrate and invade, crucial for metastatic dissemination. Interestingly, neural signaling molecules, including neurotransmitters and neuropeptides, intricately regulate EMT, influencing cancer cell motility, invasiveness, and extravasation from blood vessels.[2]Neural cues can even awaken dormant cancer cells in distant organs, sparking renewed metastatic growth.


Exploring the potential therapeutic avenues offered by understanding the intricate interplay between the nervous system and cancer is crucial. Targeting neural signaling pathways, disrupting communication between tumors and neurons, and modulating neural activity stand out as promising strategies. This burgeoning field could potentially revolutionize cancer therapy, akin to the transformative impact of immunotherapy, leading us to a more profound understanding of cancer progression and novel treatment approaches.


The convergence of neuroscientific insights and immunological advancements heralds a transformative era in cancer treatment—neuroimmunotherapy. Immune checkpoint inhibitors, exemplified by anti-PD-1 and anti-CTLA-4 antibodies, unleash the immune system's potential against cancer cells. Cancer vaccines, such as dendritic cell-based and personalized neoantigen vaccines, harness the immune system's intrinsic ability to target cancer-specific antigens.[5] These innovative strategies, informed by neurobiology, hold promise for enhanced cancer therapy and improved patient outcomes.


The convergence of neuroscientific insights and immunological advancements heralds a transformative era in cancer treatment—neuroimmunotherapy. Immune checkpoint inhibitors, exemplified by anti-PD-1 and anti-CTLA-4 antibodies, unleash the immune system's potential against cancer cells. Cancer vaccines, such as dendritic cell-based and personalized neoantigen vaccines, harness the immune system's intrinsic ability to target cancer-specific antigens.[5] These innovative strategies, informed by neurobiology, hold promise for enhanced cancer therapy and improved patient outcomes.


Also, chronic stress plays a multifaceted role in cancer development and progression, influencing immune responses, inflammatory pathways, and tumor-related processes. Stress-related behaviors, including smoking and inflammation, contribute to tumorigenesis. The Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic Nervous System (SNS) pathways release mediators that create a tumor-promoting microenvironment.[6] Addressing chronic stress through psycho-behavioral interventions could enhance cancer therapy efficacy and overall well-being, emphasizing the interconnectedness of emotions, stress, and cancer progression.


Intricately weaving together the nervous system and cancer biology, cancer neuroscience unravels a captivating and complex relationship. This dynamic interplay, from influencing oncogenesis and the tumor microenvironment to orchestrating metastatic dissemination, underscores the vital role of the nervous system in cancer progression. Through a deeper understanding of these neural-tumor interactions, novel therapeutic opportunities come to light, promising improved patient outcomes and an enriched quality of life. In this juncture of scientific exploration, innovation, and determination, the fusion of neuroscience and oncology shapes a transformative path toward a brighter future.


This article is written by Dr. Eriona Ferati (MBBS)


Reference


1. Mancusi, R., & Monje, M. (2023). The neuroscience of cancer. Nature, 597(7877), 491-492. https://doi.org/10.1038/s41586-023-05968-y


2. Amack, J. D. (2021). Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development. Cellular and Molecular Life Sciences. Advance online publication. DOI: 10.1007/s00018-021-03880-0


3. Winkler, F., Venkatesh, H. S., Amit, M., Batchelor, T., Demir, I. E., Deneen, B., Gutmann, D. H., Hervey-Jumper, S., Kuner, T., Mabbott, D., Platten, M., Rolls, A., Sloan, E. K., Wang, T. C., Wick, W., Venkataramani, V., & Monje, M. (2023). Cancer neuroscience: State of the field, emerging directions. Cell, 184(1), 1-23. Retrieved from: https://doi.org/10.1016/j.cell.2023.01.004


4. Monje, M., Borniger, J. C., D’Silva, N. J., Deneen, B., Dirks, P. B., Fattahi, F., Frenette, P. S., Garzia, L., Gutmann, D. H., Hanahan, D., Hervey-Jumper, S. L., Hondermarck, H., Hurov, J. B., Kepecs, A., Knox, S. M., Lloyd, A. C., Magnon, C., Saloman, J. L., Segal, R. A., Sloan, E. K., Sun, X., Taylor, M. D., Tracey, K. J., Trotman, L. C., Tuveson, D. A., Wang, T. C., White, R. A., & Winkler, F. (2020). Roadmap for the emerging field of cancer neuroscience. Cell, 181(2), 219-222. Retrieved from: https://doi.org/10.1016/j.cell.2020.03.034


5. Liu, J., Fu, M., Wang, M., Wan, D., Wei, Y., & Wei, X. (2022). Cancer vaccines as promising immuno-therapeutics: Platforms and current progress. Journal of Hematology & Oncology, 15, 28. Retrieved from: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01247-x


6. Wang, W., Li, L., Chen, N., Niu, C., Li, Z., Hu, J., & Cui, J. (2020). Nerves in the tumor microenvironment: Origin and effects. Frontiers in Cell and Developmental Biology, 8, 601738. DOI: 10.3389/fcell.2020.601738


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