Neurobiology of cancer: Unraveling the roles of the nervous system in tumor initiation, progression, and therapeutic

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ABSTRACT: Accumulating evidence highlights a complex interplay between the nervous system and cancer; the nervous system has a significant influence on tumor progression. This review explores the burgeoning field of neuro-oncology, focusing on the nervous system's role in tumor initiation, growth, invasion, metastasis, and treatment response. In most cases, the nervous system interacts with the tumor microenvironment (TME) through its extensive and highly intricate network at both the local and systemic levels, thereby promoting malignant behaviors such as tumor growth, invasion, and metastasis. Conversely, in certain tumor types, neural-tumor interactions may suppress tumor progression. This bidirectional regulatory phenomenon highlights the complex and diverse role of the nervous system in tumor development. Within the TME, the nervous system influences tumor progression through multiple mechanisms, including synaptic connections, paracrine signaling, and immune regulation. Studies show that in brain tumors, neurons and glial cells can promote tumor growth and treatment resistance through neurotransmitter release, synaptic signaling, and inflammatory modulation, whereas in peripheral tumors, autonomic and sensory nerve activity also regulates tumor progression. Understanding these interactions enhances our comprehension of tumor biology and enables the development of innovative therapeutic strategies targeting neuro-cancer interfaces. This interdisciplinary approach, integrating neuroscience, immunology, and oncology, provides insights into cancer-nervous system dynamics, and holds promising potential to advance the development of effective anticancer therapies.