Abstract
Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.
Highlights
Coming from the Greek words ‘kakos’ and ‘hexis’, cachexia means ‘bad condition’ and has been clinically described as long as 2000 years ago by Hippocrates.[1–7] Cachexia is a multifactorial syndrome associated with numerous chronic or end stage diseases, such as cancer, acquired immunodeficiency syndrome (AIDS), congestive heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis and tuberculosis among others.[2,5,7–11]Cachexia is a complex systemic disease, involving several metabolic pathways in different tissues and organs, and is characterized by systemic inflammation, progressive weight loss and depletion of adipose tissue and skeletal muscle that cannot be fully reversed by conventional nutritional support.[2,3,7,12–16]Metabolically, there is resistance to anabolic signals, an overall catabolic state and a negative energy balance.[15]
Weight loss is a key feature of cachexia, it is important to emphasize that its wasting process is remarkably different from starvation-associated wasting.[15]
Sarcopenia, anorexia and asthenia can be defined as distinct clinical conditions, they share multiple important common points and a certain degree of overlap (Figure 4 and Table 1)
Summary
Coming from the Greek words ‘kakos’ and ‘hexis’, cachexia means ‘bad condition’ and has been clinically described as long as 2000 years ago by Hippocrates.[1–7] Cachexia is a multifactorial syndrome associated with numerous chronic or end stage diseases, such as cancer, acquired immunodeficiency syndrome (AIDS), congestive heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis and tuberculosis among others.[2,5,7–11]. Aging is associated with a chronic state of systemic lowgrade inflammation, characterized by increased plasma levels of pro-inflammatory mediators like TNF-α and IL-6, which are able to stimulate proteolysis mainly via UPR, as previously described for cancer cachexia.[154,156–162]. There are numerous other factors that contributing to asthenia in cancer patients including anaemia, infection, muscle abnormalities/immobility, chemotherapy and/or radiotherapy, metabolic problems, cytokines, psychological distress and pain/drug side effects.[17,229]. - Loss of weight (with or without loss of fat mass) - With or without loss of appetite - Inflammation - Negative protein and energy balance - Skeletal muscle wasting - Lipolysis and browning of adipose tissue - Impaired regeneration of muscle cells - Mitochondrial dysfunction - Disruption of neuronal pathways - Acute-phase response - Malabsorption. The most two used scales are ECOG-PS and KPS. - Subjective assessment of fatigue through questionnaires
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