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Bleach R, Sherlock M, O'Reilly MW, et al. Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers. Front Cell Dev Biol. 2021;9:630503doi: 10.3389/fcell.2021.630503.
Bleach, R., Sherlock, M., O'Reilly, M. W., & McIlroy, M. (2021). Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers. Frontiers in cell and developmental biology, 9630503. https://doi.org/10.3389/fcell.2021.630503
Bleach, Rachel, et al. "Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers." Frontiers in cell and developmental biology vol. 9 (2021): 630503. doi: https://doi.org/10.3389/fcell.2021.630503
Bleach R, Sherlock M, O'Reilly MW, McIlroy M. Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers. Front Cell Dev Biol. 2021 Mar 18;9:630503. doi: 10.3389/fcell.2021.630503. eCollection 2021. PMID: 33816477; PMCID: PMC8012538.
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Front Cell Dev Biol. 2021 Mar 18;9:630503. doi: 10.3389/fcell.2021.630503. eCollection 2021.

Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers.

Frontiers in cell and developmental biology

Rachel Bleach, Mark Sherlock, Michael W O'Reilly, Marie McIlroy

Affiliations

  1. Endocrine Oncology Research Group, Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  2. Academic Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland.

PMID: 33816477 PMCID: PMC8012538 DOI: 10.3389/fcell.2021.630503

Abstract

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.

Copyright © 2021 Bleach, Sherlock, O’Reilly and McIlroy.

Keywords: IGF; cancer; endocrine; metabolism; sex steroids

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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