Neurobiology of cancer: Definition, historical overview, and clinical implications.

Studies published in the last two decades have clearly demonstrated that the nervous system plays a significant role in carcinogenesis, the progression of cancer, and the development of metastases. These studies, combining oncological and neuroscientific approaches, created the basis for the emergence of a new field in oncology research, the so-called "neurobiology of cancer." The concept of the neurobiology of cancer is based on several facts: (a) psychosocial factors influence the incidence and progression of cancer diseases; (b) the nervous system affects DNA mutations and oncogene-related signaling; (c) the nervous system modulates tumor-related immune responses; (d) tumor tissues are innervated; (e) neurotransmitters released from nerves innervating tumor tissues affect tumor growth and metastasis; (f) alterations or modulation of nervous system activity affects the incidence and progression of cancers; (g) tumor tissue affects the nervous system. The aim of this review is to characterize the pillars that create the basis of cancer neurobiology, to describe recent research advances of the nervous system's role in cancer diseases, and to depict potential clinical implications for oncology.