New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia

Cachexia is a frequent feature of chronic diseases. This syndrome includes loss of body weight, depletion of skeletal muscle mass and altered metabolic homeostasis. Acceleration of protein and energy metabolism, impaired myogenesis, and systemic inflammation contribute to cachexia. Its occurrence impinges on treatment tolerance and on the quality of life of the patient, however, no effective therapy is available yet.

This review focuses on the use of histone deacetylase inhibitors as pharmacological tools to prevent or delay cachexia, with reference to muscle wasting.

Novel histone deacetylase inhibitors could be considered as exercise mimetics and this supports their use as a treatment for muscle-wasting associated diseases, such as cachexia. The ability of some of these inhibitors to modulate the release of extracellular vesicles from tumor cells is a potential tool for restricting the development of cancer-induced muscle protein depletion. There are few clinical trials that are testing histone deacetylase inhibitors as a treatment for cachexia; this reflects the lack of robust experimental evidence of effectiveness. The determination of the pathogenic mechanisms of muscle wasting and the identification of suitable histone deacetylase inhibitors that target such mechanisms are necessary.