Mechanisms of anorexia–cachexia syndrome and rational for treatment with selective ghrelin receptor agonist

Espósito, Angela; Criscitiello, Carmen; Gelao, Lucia; Pravettoni, Gabriella; Locatelli, M.; Minchella, Ida; Leo, Mauro Di; Liuzzi, Rita; Milani, Alessandra; Massaro, Maria; Curigliano, Giuseppe

doi:10.1016/j.ctrv.2015.09.002

Cited by 31 publications

(18 citation statements)

References 32 publications

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“…108,109 Ghrelin induces the release of growth hormone (GH), stimulates appetite, regulates energy homeostasis and decreases inflammation. 110,111 Based on the promising results obtained in several phase II studies, 112–114 anamorelin was recently tested in two large double-blind, phase III trials (ROMANA 1, n = 484; ROMANA 2, n = 495).…”

Section: Options For Prevention and Treatmentmentioning

confidence: 99%

Cancer-induced muscle wasting: latest findings in prevention and treatment

2017

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Cancer cachexia is a severe and disabling clinical condition that frequently accompanies the development of many types of cancer. Muscle wasting is the hallmark of cancer cachexia and is associated with serious clinical consequences such as physical impairment, poor quality of life, reduced tolerance to treatments and shorter survival. Cancer cachexia may evolve through different stages of clinical relevance, namely pre-cachexia, cachexia and refractory cachexia. Given its detrimental clinical consequences, it appears mandatory to prevent and/or delay the progression of cancer cachexia to its refractory stage by implementing the early recognition and treatment of the nutritional and metabolic alterations occurring during cancer. Research on the molecular mechanisms underlying muscle wasting during cancer cachexia has expanded in the last few years, allowing the identification of several potential therapeutic targets and the development of many promising drugs. Several of these agents have already reached the clinical evaluation, but it is becoming increasingly evident that a single therapy may not be completely successful in the treatment of cancer-related muscle wasting, given its multifactorial and complex pathogenesis. This suggests that early and structured multimodal interventions (including targeted nutritional supplementation, physical exercise and pharmacological interventions) are necessary to prevent and/or treat the devastating consequences of this cancer comorbidity, and future research should focus on this approach.

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Section: Options For Prevention and Treatmentmentioning

confidence: 99%

Cancer-induced muscle wasting: latest findings in prevention and treatment

2017

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“…Ghrelin receptor agonists have already been developed for the treatment of cachexia in cancer patients . Although depression and anxiety disorders may be accompanied by decreases or increases in food intake , reductions in food intake in these conditions rarely meet the level of severity that would be specifically benefited by ghrelin receptor agonism.…”

Section: Peptide Hormonesmentioning

confidence: 99%

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

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Stranahan

Suchecki

et al. 2016

J Neuroendocrinology

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The central nervous system regulates and responds to endocrine signals, and this reciprocal relationship determines emotional processing and behavioural anxiety. Although the hypothalamicpituitary-adrenal (HPA) axis remains the best-characterised system for this relationship, other steroid and peptide hormones are increasingly recognised for their effects on anxiety-like behaviour and reward. The present review examines recent developments related to the role of a number of different hormones in anxiety, including pregnane neurosteroids, gut peptides, neuropeptides and hormonal signals derived from fatty acids. Findings from both basic and clinical studies suggest that these alternative systems may complement or occlude stress-induced changes in anxiety and anxiety-like behaviour. By broadening the scope of mechanisms for depression and anxiety, it may be possible to develop novel strategies to attenuate stress-related psychiatric conditions. The targets for these potential therapies, as discussed in this review, encompass multiple circuits and systems, including those outside of the HPA axis.

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“…Thus novel strategies and new pharmacotherapies are urgently needed7. There is a growing interest in the study of ligands mimicking the appetite-enhancing effects of ghrelin to treat cachexia8. Ghrelin acts as an endogenous ligand for the growth hormone secretagogue receptor, or ghrelin receptor (GHS-R1a) and has a plethora of central and peripheral actions including the release of growth hormone from the pituitary gland91011121314.…”

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confidence: 99%

A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo

Pastor-Cavada

Pardo

Kandil

et al. 2016

Sci Rep

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Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

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Mechanisms of anorexia–cachexia syndrome and rational for treatment with selective ghrelin receptor agonist

Cited by 31 publications

References 32 publications

Cancer-induced muscle wasting: latest findings in prevention and treatment

Cancer-induced muscle wasting: latest findings in prevention and treatment

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo

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