Bleach et al 2021.pdf (1.47 MB)

Growth hormone/insulin growth factor axis in sex steroid associated disorders and related cancers.

Download (1.47 MB)
journal contribution
posted on 29.03.2021, 13:15 by Rachel Bleach, Mark Sherlock, Michael O'Reilly, Marie McIlroy
To date, almost all solid malignancies have implicated insulin-like growth factor (IGF) signalling as a driver of tumour growth. However, the remarkable level of crosstalk between sex hormones, the IGF-1 receptor (IGF-1R) and its ligands IGF-1 and 2 in endocrine driven cancers is incompletely understood. Similar to the sex steroids, IGF signalling is essential in normal development as well as growth and tissue homoeostasis, and undergoes a steady decline with advancing age and increasing visceral adiposity. Interestingly, IGF-1 has been found to play a compensatory role for both estrogen receptor (ER) and androgen receptor (AR) by augmenting hormonal responses in the absence of, or where low levels of ligand are present. Furthermore, experimental, and epidemiological evidence supports a role for dysregulated IGF signalling in breast and prostate cancers. Insulin-like growth factor binding protein (IGFBP) molecules can regulate the bioavailability of IGF-1 and are frequently expressed in these hormonally regulated tissues. The link between age-related disease and the role of IGF-1 in the process of ageing and longevity has gained much attention over the last few decades, spurring the development of numerous IGF targeted therapies that have, to date, failed to deliver on their therapeutic potential. This review will provide an overview of the sexually dimorphic nature of IGF signalling in humans and how this is impacted by the reduction in sex steroids in mid-life. It will also explore the latest links with metabolic syndromes, hormonal imbalances associated with ageing and targeting of IGF signalling in endocrine-related tumour growth with an emphasis on post-menopausal breast cancer and the impact of the steroidal milieu.

Funding

PROJECT TITLE: INVESTIGATION INTO THE ANDROGEN RECEPTOR AND THE CLINICAL RELEVANCE OF CIRCULATING ANDROGENS | Funder: Beaumont Hospital Cancer Research Trust | Grant ID: N/A

History

Comments

The original article is available at https://www.frontiersin.org

Published Citation

Bleach R, Sherlock M, O’Reilly MW, McIlroy M. Growth hormone/insulin growth factor axis in sex steroid associated disorders and related cancers. Frontiers in Cell and Developmental Biology. 2021;9:246

Publication Date

18 March 2021

Department/Unit

  • Beaumont Hospital
  • Surgery
  • School of Medicine

Research Area

  • Endocrinology
  • Cancer

Publisher

Frontiers Media SA

Version

  • Published Version (Version of Record)

Licence

Exports

Royal College of Surgeons in Ireland

Licence

Exports