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Review
. 2025 Jun;26(3):443-456.
doi: 10.1007/s11154-024-09919-4. Epub 2024 Oct 18.

Growth hormone-releasing hormone and cancer

Iacopo Gesmundo  1 , Francesca Pedrolli  1 , Renzhi Cai  2   3 , Wei Sha  2   3   4   5 , Andrew V Schally  2   3   4   5 , Riccarda Granata  6
Affiliations
Review

Growth hormone-releasing hormone and cancer

Iacopo Gesmundo et al. Rev Endocr Metab Disord. 2025 Jun.

Abstract

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.

Keywords: Cancer therapy; GHRH agonists; GHRH antagonists; GHRH receptors; Signaling pathways.

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Conflict of interest statement

Declarations. Competing interests: R.C., W.S. and A.V. Schally are inventors on the patents for GHRH analogs, assigned to the University of Miami and Veterans Affairs Medical Center. The remaining authors declare no competing interests.

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