Preclinical Investigation of the Novel Histone Deacetylase Inhibitor AR-42 in the Treatment of Cancer-Induced Cachexia.

Background: Cancer cachexia is a debilitating condition that impacts patient morbidity, mortality, and quality of life and for which effective therapies are lacking. The anticachectic activity of the novel HDAC inhibitor AR-42 was investigated in murine models of cancer cachexia.

Methods: The effects of AR-42 on classic features of cachexia were evaluated in the C-26 colon adenocarcinoma and Lewis lung carcinoma (LLC) models.

Modeling human cancer cachexia in colon 26 tumor-bearing adult mice.

Background: Muscle wasting is a profound side effect of advanced cancer. Cancer-induced cachexia decreases patient quality of life and is associated with poor patient survival. Currently, no clinical therapies exist to treat cancer-induced muscle wasting.

Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression and, in cancers, are often packaged within secreted microvesicles. The cachexia syndrome is a debilitating state of cancer that predominantly results from the loss of skeletal muscle mass, which is in part associated with apoptosis. How tumors promote apoptosis in distally located skeletal muscles has not been explored.

NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia.

Cachexia is a debilitating condition characterized by extreme skeletal muscle wasting that contributes significantly to morbidity and mortality. Efforts to elucidate the underlying mechanisms of muscle loss have predominantly focused on events intrinsic to the myofiber. In contrast, less regard has been given to potential contributory factors outside the fiber within the muscle microenvironment.