title: Antineoplastic action of growth hormone-releasing hormone (GHRH) antagonists.
abstract: Some of the antagonists of growth hormone-releasing hormone (GHRH) are able to inhibit the growth of various experimental human cancers. The antitumor effects of first antagonists seemed to be dependent mainly on the disruption of pituitary secretion of growth hormone (GH), followed by the reduction in the levels of circulating insulin-like growth factor (IGF)-1, an important growth factor for cancer cells. It seems obvious, that growth hormone deficiency (GHD) induced by GHRH antagonists with all its complications, could limit the beneficial effects of GHRH antagonists therapy, and decrease patients' quality of life. The discovery of local autocrine/paracrine production of GHRH and other related growth factors in many tumoral tissues, in combination with the wide expression of GHRH receptors on cancer cells, directed the research to the synthesis of more potent GHRH antagonists. These compounds exert strong inhibitory effects directly on tumor growth, with scarce endocrine action. The receptor-mediated mechanisms comprise complex and still not completely understood effects on intracellular signaling pathways that are strictly related to human tumorigenesis. This review summarizes recent patents and latest observations on the antineoplastic role of GHRH antagonists in human tumors with emphasis on potential therapeutic applications in clinical oncology.
authors.affiliation: Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Dr. Sterling 3 Str., 91-425, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Siejka
authors.forename: Hanna
authors.initials: H
authors.lastname: Lawnicka
authors.forename: Gabriela
authors.initials: G
authors.lastname: Melen-Mucha
authors.forename: Ewelina
authors.initials: E
authors.lastname: Motylewska
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.forename: Henryk
authors.initials: H
authors.lastname: Stepien
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D013007:Growth Hormone-Releasing Hormone