Endocrine Abstracts

Understanding the processes that govern body weight is highly relevant to clinical practice as disorders of energy homeostasis cause significant morbidity and mortality. Cachexia is a syndrome of negative energy balance where muscle and fat mass are progressively lost. It affects a high proportion of patients living with cancer and is strongly associated with both reduced tolerance to anti-cancer therapy and reduced survival. Despite this, the pathophysiology of cancer cachexia remains poorly understood and, until very recently, there has been no effective, evidenced-based treatments for cancer cachexia. A robust evidence base supports the primacy of the brain and central neuronal pathways in the control of appetitive behaviour, body weight and body composition. However, it is unclear how these key homeostatic mechanisms which regulate energy balance are perturbed in cancer cachexia. A better understanding of how the pathways controlling appetitive behaviour are subverted or affected in cachexia will bring much needed mechanistic insight into a condition with unmet clinical need. In this session I will review evidence to support the hypothesis that in cancer cachexia, tumour-derived factors, acting both independently and in concert with factors derived from non-cancer tissues, can be prime drivers of the phenotype. Acting through neural mechanisms involving appetite, subsequent changes in behaviour directly contribute to the adverse changes in body composition. I will review in particular how work from model organism systems has greatly contributed to the development of emerging therapies that target GDF-15 (Growth Differentiation Factor 15), a member of the TGF-β superfamily. I will highlight how targeting GDF15 signalling shows real potential in both ameliorating the side effects of chemotherapy and increasing body weight in cancer cachexia.