Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review

Abstract

Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.

Serum ghrelin and esophageal and gastric cancer in two cohorts in China

“…Circulating ghrelin levels also increase in the presence of low BMI and malnutrition, and ghrelin levels decrease with increasing BMI and obesity. 31 The NIT study, in particular, was undertaken in a population who could be classified as under nourished using any metric 32,33 which likely explains the higher concentrations of this orexigenic hormone in the NIT cohort (mean ghrelin 1,022 pg/ml controls), relative to Shanghai (mean ghrelin 743 pg/ml controls) or previous studies in Finland (mean ghrelin 802 pg/ml controls) 15 and Iran (median ghrelin 672 pg/ml controls). 25 Future studies investigating the association of ghrelin levels with subsequent incidence of esophageal, and other cancers, are clearly merited.…”

Cachexia and Sarcopenia in Companion Animals: An Under‐Utilized Natural Animal Model of Human Disease

“…However, ghrelin also has a effects throughout the body. Ghrelin modulates growth hormone secretion (and thus, IGF-1 production), and can have beneficial effects on muscle mass, inflammation, cardiac function, gastric motility, and many others [95]. Ghrelin concentrations are increased in people with CHF but food intake is decreased, suggesting loss of normal feedback and resistance to ghrelin [96][97][98][99].…”

Two ghrelin receptor agonists for adults with malnutrition: a systematic review and meta-analysis

“…Additionally, clinical studies with anamorelin [58] and ghrelin [59] have also shown no significant effect on overall survival compared with placebo. Long-term, large-scale clinical trials are required to determine whether treatment with ghrelin receptor agonists could stimulate tumour growth [60]. …”