Anorexia is present in up to 50% of newly diagnosed cancer patients and is the fourth most common symptom (after pain, fatigue and weakness) in patients with advanced cancer stages.

Tumour‐released substances such as proinflammatory cytokines, lactate, or PTHRP contribute decisively to anorexia

Inflammation is a major driver of cachexia, affecting the function of several tissues including skeletal muscle, fat, brain and liver.

Because of the frequency with which cachexia occurs in conjunction with anorexia, or decreased appetite, it is often referred to as the anorexia–cachexia syndrome.

have among the highest incidence of cachexia, estimated at 70%

much attention has been given to

A large body of evidence has established that cytokines, such as tumour necrosis factor-α (TNFα), transforming growth factor-β (TGFβ) and IL-6, promote muscle fibre breakdown (reviewed elsewhere3,23) (Fig. 1a)

Preclinical models and in vitro experiments have provided valuable insight into the regulation of cancer-induced muscle wasting.

Moreover, conditioned medium from Capan-1 pancreatic cancer cells, which contains abundant IGFBP-3, significantly induces muscle cell wasting. This wasting effect is potently alleviated by IGFBP3 knockdown in Capan-1 cells or IGFBP-3 antibody neutralization.

The factors that induce cachexia in pancreatic cancer are largely unknown.

We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis

Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice.

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia

There are numerous causes of anorexia in cachexia (Figure ​11).2 These can be conveniently categorized as being due to central or peripheral mechanisms. In each group, there are also a series of secondary causes due to chemotherapy.

Central causes of anorexia can be depression, pain, or a variety of alterations in central neurotransmitters.

Direct experimental evidence demonstrates that stimulating the hypothalamus with inflammatory cytokines, such as IL-1, IL-6, TNF-α, and leukemia inhibitory factor, leads to anorexia via altering the activity of POMC and AgRP neurons

Anorexia is often a major contributor to the weight loss and muscle wasting, and even with administration of drugs that target overactivation of catabolic processes and inflammation, adequate nutritional support still remains a mainstay of cachexia therapy

ding of Recommendations Assessment, Devel-opment, and Evaluation as low or very low because of indirectness, imprecision,

Anorexia is caused by ghrelin resistance, cytokine release, and a decreased hypothalamic drive to eat, but also by pain, weakness, dry mouth, difficulty chewing or swallowing, dysphagia, constipation, chemosensory disturbances (e.g., taste and smell), early satiety, and nausea. These can all contribute to reduced caloric intake

Cytokines such as TNF-α, IL-1, IL-6, and interferon-gamma (IFN-γ) are released by both cancer cells and host immune cells (macrophages/lymphocytes). These are involved in mediating the pro-inflammatory state, stress response, anorexia, sickness behavior, hypermetabolism, and accelerated breakdown of protein, muscle, and adipose tissues in cancer cachexia patients