Blocking ActRIIB and restoring appetite reverses cachexia and improves survival in mice with lung cancer.

ABSTRACT: Cancer cachexia is a common, debilitating condition with limited therapeutic options. Using an established mouse model of lung cancer, we find that cachexia is characterized by reduced food intake, spontaneous activity, and energy expenditure accompanied by muscle metabolic dysfunction and atrophy. We identify Activin A as a purported driver of cachexia and treat with ActRIIB-Fc, a decoy ligand for TGF-β/activin family members, together with anamorelin (Ana), a ghrelin receptor agonist, to reverse muscle dysfunction and anorexia, respectively. Ana effectively increases food intake but only the combination of drugs increases lean mass, restores spontaneous activity, and improves overall survival. These beneficial effects are limited to female mice and are dependent on ovarian function. In a

SUBMITTER: Queiroz AL 

PROVIDER: S-EPMC9360437 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature