Trends in Cancer
ReviewCancer Cachexia: More Than Skeletal Muscle Wasting
Section snippets
Cancer Cachexia Is a Multiorgan Syndrome
Cancer cachexia is a multifactorial condition characterized by body weight loss as a result of metabolic dysregulation and anorexia (reduced food intake; see Glossary) in the presence of a tumor disease (see Box 1 for a more detailed definition). Cancer cachexia is of clinical relevance, since it not only negatively affects the quality of life of patients with cancer, but also reduces efficacy and increases toxicity of anticancer chemotherapy, thereby strongly contributing to mortality from
Adipose Tissue: Dysfunctional Lipid Storage and Remodeling in Cachexia
While muscle wasting has traditionally been the most explored mechanism in cachexia research (Box 3), it is increasingly recognized that adipose tissue (AT) wasting represents an important component of cancer-associated weight loss. Indeed, functional AT is a key to metabolic health and plays an important role not only in cachexia but also in other wasting conditions, such as lipodystrophy, sepsis, and burn injuries [4]. The importance of AT is emphasized by the finding that AT loss often
Heart: Cachexia Affects Heart Mass and Function
In addition to the loss of skeletal muscle and usually AT, cancer cachexia is also associated with significant wasting of the heart muscle, which is accompanied by cardiac remodeling and dysfunction [31]. The clinical relevance of this cardiac manifestation of cancer cachexia is emphasized by the facts that cardiac mortality is generally increased in cancer patients, and that the detrimental effects of the malignant disease on heart mass and function can be aggravated by the cardiotoxicity of
Blood: Elevated Thrombosis Risk Might Contribute to Increased Mortality in Cancer Cachexia
It is clear that the blood plays a central role in cancer cachexia by transporting tumor- and host-derived mediators of tissue wasting, including (but not limited to) factors contributing to the systemic inflammation in cachexia as well as tumor-activated peripheral blood mononuclear cells [43]. However, in addition to facilitating tissue crosstalk in cachexia, the blood itself has also been suggested to change to a more coaguable state, which may more directly cause mortality in cachexia 44, 45
Liver: Cachexia Alters Hepatic Metabolism and Activates the Hepatic APR
Cancer cachexia is associated with changes in liver function that may promote the increased energy loss and mortality associated with this condition. It has long been known that lactate derived from tumor glycolysis is reconverted into glucose by hepatic gluconeogenesis during tumor growth. This futile cycle is energy consuming and has been proposed to account for a significant proportion of the energy loss observed in cancer patients [49]. Whether this mechanism applies to all tumor entities
Additional Tissues: Brain, Gut, Pancreas, Bone, Testes, and Ovaries
In addition to the tissues covered in detail above, cancer cachexia has also been associated with changes in function of multiple other tissues that also appear to contribute to the disease etiology, underlining the systemic nature of this phenomenon.
Due to the anorexic component of cancer cachexia, the brain has also received attention in this context [70], where hypothalamic inflammation [71] as well as activation of calcitonin gene-related peptide neurons in the parabrachial nucleus [72]
Concluding Remarks
Cancer cachexia is a multifactorial condition at two levels: (i) cachexia results from variable degrees of metabolic dysregulation and anorexia in the presence of a tumor disease; and (ii) cancer-associated wasting, as illustrated by the studies described above, is a systemic phenomenon affecting and/or influenced by various tissues as well as diverse forms of tissue crosstalk (Figure 1). Despite novel insights into the systemic nature of cancer cachexia, multiple challenges remain (see
Acknowledgments
This work was supported by the CRC/SFB824 and the CRC/SFB1321 (both DFG) to S.H. and M.B.D. and by the Novo Nordisk Foundation (NNF15OC0012345) to S.F.S..
Glossary
- Acute-phase response (APR)
- a prominent systemic reaction of the organism to local or systemic disturbances in its homeostasis caused by infection, tissue injury, trauma, surgery, neoplastic growth, or immunological disorders. It represents an unspecific and acute inflammatory response comprising the synthesis of acute-phase proteins primarily by hepatocytes, which are released into the circulation.
- Anorexia
- decreased sensation of appetite that can result in undernutrition.
- Autophagy
- a process that
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