Central neuroendocrine governance as a unifying framework for host–tumor interaction: From afferent sensing to therapeutic modulation

Abstract

Cancer is not biologically confined to the tumor bed. Cachexia, fatigue, metabolic dysfunction, circadian disruption, and immune dysfunction reflect disturbances that local models alone cannot fully explain. The brain is well positioned to participate in these processes because it continuously samples circulating signals and coordinates endocrine and autonomic responses. Yet the afferent side of this communication has received less attention than its downstream consequences. Here, we synthesize evidence showing that cytokines, hormones, metabolites, and cargo carried by extracellular vesicles can engage central sensory interfaces and integrative regions, particularly circumventricular organs and hypothalamic and brainstem circuits. We use the term Endocriception to describe afferent humoral sensing and early central decoding of circulating biochemical signals, and focus here on how tumor- and host-associated changes engage this process in cancer. Central neuroendocrine governance refers to the subsequent integration of this information and the generation of autonomic and endocrine outputs. Persistent inflammation, stress, circadian disruption, and impaired feedback may gradually reconfigure this regulatory system. The resulting changes can affect systemic immunity, metabolism, behavior, and host tolerance of cancer. Evidence is strongest for a limited number of pathways, whereas many proposed links remain incomplete or dependent on tumor type and experimental context. We therefore present central neuroendocrine governance as a working framework for organizing current evidence and guiding mechanistic studies, biomarker development, and interventions aimed at restoring host physiology.