Cancer as a homeostatic challenge: the role of the hypothalamus.

The initiation, progression, and metastatic spread of cancer elicits diverse changes in systemic physiology. In this way, cancer represents a novel homeostatic challenge to the host system. Here, we discuss how the hypothalamus, a critical brain region involved in homeostasis senses, integrates and responds to cancer-induced changes in physiology. Through this lens, cancer-associated changes in behavior (e.g., sleep disruption) and physiology (e.g., glucocorticoid dysregulation) can be viewed as the result of an inability to re-establish homeostasis. We provide examples at each level (receptor sensing, integration of systemic signals, and efferent regulatory pathways) of how homeostatic organization becomes disrupted across different cancers. Finally, we lay out predictions of this hypothesis and highlight outstanding questions that aim to guide further work in this area. Cancer represents a homeostatic challenge to the host system. The brain detects cancer-induced changes in physiology via multiple receptor modalities present on afferent nerves, as well as centrally within the hypothalamus and other brain structures. Integration of peripheral signals elicits downstream changes in neuronal output. The hypothalamus attempts to restore homeostasis via the HPA axis and autonomic nervous system. Failure to restore homeostasis can result in deleterious phenotypes associated with cancer, such as blunted glucocorticoid responses and sleep/wake disruption. [ABSTRACT FROM AUTHOR]