Systemic Regulation of Cancer Development by Neuro-Endocrine-Immune Signaling Network at Multiple Levels

Abstract

The overarching view of current tumor therapies simplifies cancer to a cell-biology problem in which neoplasms are caused solely by malignant cells and the exploration of carcinogenesis and tumor progression largely focuses on somatic mutations and other genetic abnormalities of cancer cells. The limited therapeutic response indicates that cancer is driven not only by endogenous oncogenic factors and reciprocal interactions within the tumor microenvironment, but also by complex systemic processes. Homeostasis is the fundamental premise of health, and is maintained by systemic regulation of neuro-endocrine-immune axis. Cancer is also a systemic disease that manifested by dysfunction of the nervous, endocrine, and immune systems. Multiple axes of regulation exist in cancer, including central-, organ-, and microenvironment-level manipulation. At each specific regulatory level, the tridirectional communication among the nervous, endocrine, and immune factors transmit flexible signaling to induce proliferation, invasion, reprogrammed metabolism, therapeutic resistance, and other malignant phenotypes of cancer cells, resulting in the extremely poor prognosis of this lethal disease. Understanding this coordinated signaling network will enable the development of new approaches for cancer treatment via behavioral and pharmacological interventions.

Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis

“…Pulmonary neuroepithelial bodies (NEB) are innervated serotonin (5-HT)-producing cells distributed throughout the airway epithelium. Studies have reported that 5-HT secretion can stimulate cancer progression, including cancer proliferation, migration, and invasion [ 20 , 21 ]. The data in Figure 1 provide evidence that AZ, SFN, and their combination show dose-dependent reduction in scratch wound closure by the bronchial carcinoid H727 (typical carcinoid) cells.…”

Emerging Trends on the Correlation Between Neurotransmitters and Tumor Progression in the Last 20 Years: A Bibliometric Analysis via CiteSpace

“…The explored connection between the nervous system and tumor tissue is not surprising, as they share a reciprocal impact. On the one hand, nerve fibers or neurotransmitters in tumor tissues not only can act on fibroblasts in the microenvironment by modulating the extracellular matrix synthesis or shaping synaptic-like connections with tumor cells ( 30 ) but also has a direct effect on immune cells, thereby regulating the infiltration of immune cells into tumors ( 7 , 8 ). On the other hand, the invasion of the surrounding nerves by cancer cells also provides a route for metastasis and promotes tumorigenesis via the crosstalk between neuron cells and tumor cells ( 31 , 32 ).…”

“…As important messengers of neural signaling, neurotransmitters and their receptors contribute to tumor proliferation, angiogenesis and tumor metastasis (3)(4)(5)(6). Additionally, neurotransmitter receptors are widely expressed on the surface of immune cells and regulated by their corresponding neurotransmitters, thus affecting tumor immune responses (7,8).…”

Antitumoral and Anti-inflammatory Roles of Somatostatin and Its Analogs in Hepatocellular Carcinoma

“…The importance of neuroendocrine factors in various cancers has been emphasized in recent research [ 30 , 37 , 38 ]. Studies on somatostatin, ever since its discovery, have demonstrated its inhibitory effects on the secretion of numerous hormones, as mentioned above.…”