Growth hormone-releasing hormone and cancer.

Autor: Gesmundo I; Department of Medical Sciences, University of Turin, Turin, Italy., Pedrolli F; Department of Medical Sciences, University of Turin, Turin, Italy., Cai R; Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, USA.; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA., Sha W; Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, USA.; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Pathology, School of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller, Miami, FL, USA., Schally AV; Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL, USA.; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Pathology, School of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller, Miami, FL, USA., Granata R; Department of Medical Sciences, University of Turin, Turin, Italy. riccarda.granata@unito.it.
Jazyk: angličtina
Zdroj: Reviews in endocrine & metabolic disorders [Rev Endocr Metab Disord] 2024 Oct 18. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1007/s11154-024-09919-4
Abstrakt: The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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