Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet.

Abstract

Systemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed. Clinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development. The adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients' function and quality of life, protection/mitigation of these side effects is a research priority.