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.