Involuntary weight loss is one of the hallmarks of advanced cancer. Healthy adults are generally highly resistant to attempts to lose body fat, which stores a remarkably constant amount of energy overall. Normally, highly precise controls work to ensure that energy expenditure and energy intake are matched (energy homeostasis), so that there is neither net loss nor net gain of body energy stores. In the patient with advanced cancer, however, a failure to maintain food intake relative to energy expenditure results in a failure to maintain energy homeostasis and is a primary contributor to involuntary weight loss. Reported levels of food intake in weight-losing patients with cancer are often lower than the basal metabolic rate of the same or similar patient populations.

A full understanding of this weight loss is intimately linked to an understanding of the factors coordinating the balance between food intake and energy expenditure. Body weight is controlled by centers in the brain, notably the hypothalamus. Specific hypothalamic nuclei integrate cognitive, visual, taste, and olfactory sensory inputs, as well as peripheral signals indicating the status of physiological reserves of energy and protein in the whole body, the activity of the gastrointestinal tract, and nutrient intake. Three main elements of the appetite regulatory systems are considered here: the hypothalamic control of appetite, the reward pathway, and the sensory inputs that support food intake.