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Barriers to cancer nutrition therapy: excess catabolism of muscle and adipose tissues induced by tumour products and chemotherapy

  • Dalton L. Schiessel (a1) and Vickie E. Baracos (a2)

Abstract

Cancer-associated malnutrition is driven by reduced dietary intake and by underlying metabolic changes (such as inflammation, anabolic resistance, proteolysis, lipolysis and futile cycling) induced by the tumour and activated immune cells. Cytotoxic and targeted chemotherapies also elicit proteolysis and lipolysis at the tissue level. In this review, we summarise specific mediators and chemotherapy effects that provoke excess proteolysis in muscle and excess lipolysis in adipose tissue. A nutritionally relevant question is whether and to what degree these catabolic changes can be reversed by nutritional therapy. In skeletal muscle, tumour factors and chemotherapy drugs activate intracellular signals that result in the suppression of protein synthesis and activation of a transcriptional programme leading to autophagy and degradation of myofibrillar proteins. Cancer nutrition therapy is intended to ensure adequate provision of energy fuels and a complete repertoire of biosynthetic building blocks. There is some promising evidence that cancer- and chemotherapy-associated metabolic alterations may also be corrected by certain individual nutrients. The amino acids leucine and arginine provided in the diet at least partially reverse anabolic suppression in muscle, while n-3 PUFA inhibit the transcriptional activation of muscle catabolism. Optimal conditions for exploiting these anabolic and anti-catabolic effects are currently under study, with the overall aim of net improvements in muscle mass, functionality, performance status and treatment tolerance.

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Corresponding author

*Corresponding author: V. E. Baracos, email vickie.baracos@ualberta.ca

References

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