Clinical development of ghrelin axis-derived molecules for cancer cachexia treatment

Abstract

Cachexia is a devastating complication of cancer for which there is no approved treatment. Here we review the clinical development of ghrelin and ghrelin mimetics (also known as growth hormone secretagogues or GHS) for cancer cachexia treatment. Ghrelin, a novel hormone known to increase appetite, lean and fat mass, and growth hormone secretion, is being developed as a therapeutic option for cancer anorexia-cachexia syndrome (CACS). Recent animal studies suggest that it may also decrease inflammation and that some of its effects may be independent of its only known receptor, the GHS receptor-1a.Clinical studies recently have shown that administration of ghrelin or GHS improves appetite and quality of life as assessed by questionnaires. Weight gain, increased food intake and better tolerance to chemotherapy have also been reported. This treatment appears to be safe and well tolerated. Ghrelin and GHS have the potential to effectively prevent or reverse CACS. Preliminary studies show improvements in weight stabilization and appetite with short-term usage. Further studies are required to fully characterize the role of ghrelin and GHS for the treatment of CACS and to establish the safety of this approach.