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Therapeutic Targeting of the IGF Axis

The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF sign...

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Autores principales: Osher, Eliot, Macaulay, Valentine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721736/
https://www.ncbi.nlm.nih.gov/pubmed/31416218
http://dx.doi.org/10.3390/cells8080895
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author Osher, Eliot
Macaulay, Valentine M.
author_facet Osher, Eliot
Macaulay, Valentine M.
author_sort Osher, Eliot
collection PubMed
description The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF signaling in the pathogenesis of cancer, endocrine disorders including acromegaly, diabetes and thyroid eye disease, skin diseases such as acne and psoriasis, and the frailty that accompanies aging. We discuss the use of IGF axis inhibitors, focusing on the different approaches that have been taken to develop effective and tolerable ways to block this important signaling pathway. We outline the advantages and disadvantages of each approach, and discuss progress in evaluating these agents, including factors that contributed to the failure of many of these novel therapeutics in early phase cancer trials. Finally, we summarize grounds for cautious optimism for ongoing and future studies of IGF blockade in cancer and non-malignant disorders including thyroid eye disease and aging.
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spelling pubmed-67217362019-09-10 Therapeutic Targeting of the IGF Axis Osher, Eliot Macaulay, Valentine M. Cells Review The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF signaling in the pathogenesis of cancer, endocrine disorders including acromegaly, diabetes and thyroid eye disease, skin diseases such as acne and psoriasis, and the frailty that accompanies aging. We discuss the use of IGF axis inhibitors, focusing on the different approaches that have been taken to develop effective and tolerable ways to block this important signaling pathway. We outline the advantages and disadvantages of each approach, and discuss progress in evaluating these agents, including factors that contributed to the failure of many of these novel therapeutics in early phase cancer trials. Finally, we summarize grounds for cautious optimism for ongoing and future studies of IGF blockade in cancer and non-malignant disorders including thyroid eye disease and aging. MDPI 2019-08-14 /pmc/articles/PMC6721736/ /pubmed/31416218 http://dx.doi.org/10.3390/cells8080895 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Osher, Eliot
Macaulay, Valentine M.
Therapeutic Targeting of the IGF Axis
title Therapeutic Targeting of the IGF Axis
title_full Therapeutic Targeting of the IGF Axis
title_fullStr Therapeutic Targeting of the IGF Axis
title_full_unstemmed Therapeutic Targeting of the IGF Axis
title_short Therapeutic Targeting of the IGF Axis
title_sort therapeutic targeting of the igf axis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721736/
https://www.ncbi.nlm.nih.gov/pubmed/31416218
http://dx.doi.org/10.3390/cells8080895
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