Skeletal muscle atrophy in cancer cachexia : from mechanistic exploration to novel therapeutic perspectives

Muscle wasting during cancer is clearly recognized as a factor of poor prognostic. According to preclinical studies, preserving muscle mass allows to extend survival and therefore appears to be a major therapeutic goal in oncology. As approved treatments are still lacking, we aimed to study the mechanisms underlying muscle atrophy to further identify new therapeutic strategies. First, we evidenced marked remodeling of muscle proteome during cancer cachexia, with a release of inflammatory proteins, which is closely related to the cachexia progression. We then investigated the role of an anti-inflammatory adipokine, adiponectin, whose levels are markedly reduced during cancer. We showed that restoring pharmacologically adiponectin signaling, with a synthetic agonist of adiponectin receptors, AdipoRon, rescued the cachectic phenotype by alleviating body weight loss and muscle atrophy, along with restraining inflammation and hypercorticism in preclinical murine models. AdipoRon could thus represent an innovative therapeutic strategy to counteract cancer cachexia.