Figure 4.

The impact of anti-cancer chemotherapy treatment on cachectic myopathy and possible protective therapeutic interventions. Broadly, chemotherapeutic agents used in clinical cancer treatment can both directly and indirectly target skeletal muscle through induction or amplification of systemic cachexia. The result is the initiation of a wasting and dysfunction program within skeletal muscle, involving: increased muscle protein degradation, reduced protein synthesis, mitochondrial dysfunction and oxidative stress, cytoskeletal disorganisation and reduction of key cytoskeletal proteins that stabilise the muscle membrane, pro-fibrotic signalling within the extracellular matrix, and altered calcium (Ca2+) dynamics. The result is muscle wasting and dysfunction that leaves patients weak and fatigued, which affects their capacity to undertake activities of daily living and reduces quality of life. Several potential therapeutic approaches are currently being investigated to protect against or treat these symptoms including appetite stimulants, activin receptor signalling inhibitors, nutritional supplements, and phytotherapies. Novel therapeutic strategies could include exercise and mitoprotective compounds (e.g., SS-31, BGP-15, dimethyl fumarate (DMF), epicatechin, and pterostilbene). Abbreviations: CNS AIR: central nervous system acute illness response. Created with biorender.com (accessed on 6 July 2021).