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Systemic Regulation of Cancer Development by Neuro-Endocrine-Immune Signaling Network at Multiple Levels
Shu-Heng Jiang1, Xiao-Xin Zhang1, Li-Peng Hu1
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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.
Insights
Cancer is a systemic disease, not just a cellular one, involving complex interactions between the nervous, endocrine, and immune systems. Understanding this neuro-endocrine-immune axis is key to developing new cancer therapies.
Area of Science:
- Oncology
- Systems Biology
- Immunology
Background:
- Current cancer therapies often focus solely on malignant cells and genetic abnormalities.
- Limited therapeutic responses suggest cancer involves more than just cellular factors and the tumor microenvironment.
- Health relies on homeostasis maintained by the neuro-endocrine-immune axis, which is disrupted in cancer.
Purpose of the Study:
- To reframe cancer as a systemic disease involving the nervous, endocrine, and immune systems.
- To explore the tridirectional communication within the neuro-endocrine-immune axis in cancer regulation.
- To identify potential therapeutic targets through understanding this coordinated signaling network.
Main Methods:
- Analysis of existing literature on cancer biology and systemic regulation.
- Conceptual framework development integrating cellular, microenvironmental, and systemic factors.
- Review of neuro-endocrine-immune interactions in the context of carcinogenesis and tumor progression.
Main Results:
- Cancer involves complex systemic processes beyond cellular genetics, disrupting homeostasis.
- The nervous, endocrine, and immune systems communicate bidirectionally at multiple regulatory levels (central, organ, microenvironment).
- This communication network drives cancer cell proliferation, invasion, metabolic reprogramming, and therapeutic resistance.
Conclusions:
- Cancer is a systemic disease characterized by neuro-endocrine-immune axis dysfunction.
- Targeting the coordinated signaling network of the nervous, endocrine, and immune systems offers novel therapeutic strategies.
- Behavioral and pharmacological interventions modulating these axes may improve cancer treatment outcomes.
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