International collaborative research led by Dr Kate Murphy discovers promising adjunct therapy for cancer cachexia
Dr Kate Murphy (Dept. Physiology, Centre for Muscle Research) has led a long-term study on the therapeutic potential of Mas receptor (MasR) activation for cancer and other serious muscle wasting conditions.
'Mas receptor activation slows tumour growth and attenuates muscle wasting in cancer' was published in the journal Cancer Research late in 2018. The work involved a wonderful collaboration with researchers at the University of Florida (Gainesville, FL, USA).
Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. Cachexia robs patients of their strength and capacity to perform daily tasks and live independently. Effective treatments are needed urgently. Here we investigated the therapeutic potential of activating the 'alternative' axis of the Renin-Angiotensin System (RAS), involving ACE2, angiotensin-(1-7), and the mitochondrial assembly receptor (MasR), for treating cancer cachexia. Plasmid overexpression of the MasR or pharmacological angiotensin-(1-7)/MasR activation did not affect healthy muscle fiber size in vitro or in vivo but attenuated atrophy induced by co-culture with cancer cells in vitro. In mice with cancer cachexia, the MasR agonist AVE 0991 slowed tumor development, reduced weight loss, improved locomotor activity, and attenuated muscle wasting, with the majority of these effects dependent on the orexigenic and not anti-tumor properties of AVE 0991. Proteomic profiling and immunohistochemistry revealed that mechanisms underlying AVE 0991 effects on skeletal muscle involved miR-23a-regulated preservation of the fast, glycolytic fibers. MasR activation is a novel regulator of muscle phenotype and AVE 0991 has orexigenic, anti-cachectic and anti-tumorigenic effects, identifying it as a promising adjunct therapy for cancer and other serious muscle wasting conditions.
Read the study published in Cancer Research here.