Potential Inflammatory Mechanisms Underlying Chemotherapy-Induced Peripheral Neuropathy and Skeletal Muscle Effects
- Pp. 173-201 (29)Claire E. Feather, John B. Kwok, Gila Moalem-Taylor and Patsie Polly
Cancer patients receiving chemotherapy treatment frequently experience adverse side effects, including the development of chemotherapy-induced peripheral neuropathy (CIPN) and muscle wasting. Investigation into the pathophysiological mechanisms responsible for these neuromuscular effects is crucial since associated symptoms including pain and muscle fatigue can lead to chemotherapy dose reduction or discontinuation, as well as long-term effects on patient mobility and quality of life. While patient symptoms may vary depending on the chemotherapy drug type and dosage regime, inflammation has been implicated as a common mediator responsible for the peripheral tissue effects associated with chemotherapy use. Although mitochondrial dysfunction has been recently investigated as a key underlying mechanism of CIPN and chemotherapy-induced muscle atrophy, there is a close association between mitochondrial dysfunction, oxidative stress and inflammation in biological systems. Host genetic factors have also been implicated in CIPN, and further genetic studies are therefore essential for identifying biomarkers of patient susceptibility, as well as assisting in the elucidation of candidate molecular pathways. Finally, another important consideration is the relationship between cancer-induced and chemotherapy-induced effects, given that chemotherapy can exacerbate cancer cachexia-related muscle wasting. Since cancer cachexia results from excessive systemic inflammation due to the host-tumour interaction, these findings suggest that inflammation-associated molecular alterations due to chemotherapy administration could contribute to muscle wasting in the treatment setting. Therefore, the purpose of this chapter is to provide evidence for a role of inflammation in chemotherapy-induced neuromuscular effects, and to summarise recent patented developments aimed at targeting these side effects.