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.
Keywords: Cancer cachexia, cancer treatment, chemotherapy-induced peripheral
neuropathy, inflammation, inflammatory cytokines, mitochondrial dysfunction,
muscle wasting, reactive oxygen species, skeletal muscle atrophy.
