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Review
. 2021 Aug 7;13(16):3990.
doi: 10.3390/cancers13163990.

Neural Mechanisms of Cancer Cachexia

Brennan Olson  1   2 , Parham Diba  1   2 , Tetiana Korzun  1   2 , Daniel L Marks  2   3
Affiliations
Review

Neural Mechanisms of Cancer Cachexia

Brennan Olson et al. Cancers (Basel). .

Abstract

Nearly half of cancer patients suffer from cachexia, a metabolic syndrome characterized by progressive atrophy of fat and lean body mass. This state of excess catabolism decreases quality of life, ability to tolerate treatment and eventual survival, yet no effective therapies exist. Although the central nervous system (CNS) orchestrates several manifestations of cachexia, the precise mechanisms of neural dysfunction during cachexia are still being unveiled. Herein, we summarize the cellular and molecular mechanisms of CNS dysfunction during cancer cachexia with a focus on inflammatory, autonomic and neuroendocrine processes and end with a discussion of recently identified CNS mediators of cachexia, including GDF15, LCN2 and INSL3.

Keywords: GDF15; INSL3; LCN2; autonomic nervous system; cachexia; cancer; cytokines; neuroendocrinology; neuroinflammation.

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Conflict of interest statement

D.L.M. is a consultant for Pfizer, Inc. and Alkermes, Inc. D.L.M. is a consultant, has received grant funding and has equity in Tensive Controls, Inc. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Model of CNS amplification of peripheral inflammatory signals during the evolution of cancer cachexia.
Figure 2
Figure 2
Model and potential mechanisms of sympathetic nervous system engagement in the pathogenesis of cancer.
Figure 3
Figure 3
Model and potential mechanisms of hypothalamic–pituitary–adrenal/gonadal axes in the pathogenesis of cancer cachexia.
Figure 4
Figure 4
Graphical representation of cachexia-inducing effects of GDF15, LCN2 and INSL3 after binding to their respective receptors in the brain.
See this image and copyright information in PMC

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