Growth Hormone-Releasing Hormone Dynamics in Cancer Therapy

Growth hormone-releasing hormone (GHRH) is classically known for its role in stimulating pituitary growth hormone secretion but has emerged as a key modulator in oncogenesis. Many tumours express GHRH receptors (GHRH-R) and engage in autocrine and paracrine GHRH signalling to drive proliferation, survival and angiogenesis. Antagonists of GHRH-R have been demonstrated to suppress tumour growth by interrupting the GHRH–IGF-1 axis, downregulating pro-inflammatory cytokine networks and inhibiting downstream mitogenic pathways such as ERK and PI3K/AKT. Synthetic agonists and antagonists exhibit distinct pharmacokinetic profiles, allowing fine-tuning of receptor engagement for either antitumour or tissue-protective outcomes. In preclinical models of breast, lung, gastric and pancreatic cancers, GHRH antagonists reduce xenograft volume, diminish expression of inflammatory mediators and attenuate metastatic potential. Moreover, combinatorial approaches pairing GHRH antagonists with conventional chemotherapeutics or immune-checkpoint inhibitors show amplified efficacy and improved tolerability. The interplay between GHRH signalling and immune cell differentiation further suggests potential for modulation of tumour microenvironments. Overall, targeting GHRH dynamics offers a multi-faceted strategy that integrates endocrine, inflammatory and growth-factor pathways to combat refractory malignancies and enhance therapeutic indices across diverse cancer types.

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Growth Hormone-Releasing Hormone Dynamics in Cancer Therapy publication trend

The graph below shows the total number of articles in growth hormone-releasing hormone dynamics in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Growth Hormone-Releasing Hormone (GHRH): A hypothalamic peptide that stimulates pituitary growth hormone release and functions in tumour autocrine/paracrine loops.

GHRH Receptor (GHRH-R): A G-protein-coupled receptor expressed in pituitary and various cancers, mediating mitogenic and inflammatory signals.

GHRH Antagonist: A synthetic analog that blocks GHRH-R activation, inhibiting downstream proliferative and cytokine pathways.

GHRH Agonist: A peptide mimetic that stimulates GHRH-R, used to modulate IGF-1 secretion and tissue-protective responses.

IGF-1 Axis: An endocrine network centred on insulin-like growth factor-1 that promotes cell growth and survival, often co-opted by tumours.

References

1. Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers. Oncotarget (2012).
2. Growth hormone-releasing hormone (GHRH) and its agonists inhibit hepatic and tumoral secretion of IGF-1. Oncotarget (2018).
3. Synthesis of potent antagonists of receptors for growth hormone-releasing hormone with antitumor and anti-inflammatory activity. Peptides (2021).