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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Vydáno v:Cells (Basel, Switzerland) Ročník 8; číslo 8; s. 895
Hlavní autoři: Osher, Eliot, Macaulay, Valentine M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 14.08.2019
MDPI
Témata:
Acne
Acromegaly
Aging
Aging - metabolism
Animals
Binding sites
Biological activity
Cancer
Cancer therapies
Diabetes mellitus
Dwarfism
Endocrine disorders
Endocrine System Diseases - drug therapy
Endocrine System Diseases - metabolism
Eye diseases
Gene amplification
Growth factors
Humans
IGF
IGF inhibitor
IGF-1R
Insulin
Insulin-like growth factors
Kinases
Ligands
Medical prognosis
Metastasis
Mice
Molecular Targeted Therapy
Mutation
Neoplasms - drug therapy
Neoplasms - metabolism
ophthalmopathy
Prostate cancer
Proteins
Psoriasis
Rats
Receptor, IGF Type 1 - antagonists & inhibitors
Review
Signal transduction
Signal Transduction - drug effects
Skin diseases
Skin Diseases - drug therapy
Skin Diseases - metabolism
Somatomedins - antagonists & inhibitors
Therapeutic targets
Thyroid
Tumors
type 1 IGF receptor
IGF inhibitor
type 1 IGF receptor
IGF
ophthalmopathy
acromegaly
cancer
IGF-1R
ISSN:2073-4409, 2073-4409
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Abstract 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.
AbstractList 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.
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.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.
Author Osher, Eliot
Macaulay, Valentine M.
AuthorAffiliation Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK
AuthorAffiliation_xml – name: Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK
Author_xml – sequence: 1
  givenname: Eliot
  surname: Osher
  fullname: Osher, Eliot
– sequence: 2
  givenname: Valentine M.
  surname: Macaulay
  fullname: Macaulay, Valentine M.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31416218$$D View this record in MEDLINE/PubMed
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Issue 8
Keywords IGF inhibitor
type 1 IGF receptor
IGF
ophthalmopathy
acromegaly
cancer
IGF-1R
Language English
License 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/).
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Snippet The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to...
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StartPage 895
SubjectTerms Acne
Acromegaly
Aging
Aging - metabolism
Animals
Binding sites
Biological activity
Cancer
Cancer therapies
Diabetes mellitus
Dwarfism
Endocrine disorders
Endocrine System Diseases - drug therapy
Endocrine System Diseases - metabolism
Eye diseases
Gene amplification
Growth factors
Humans
IGF
IGF inhibitor
IGF-1R
Insulin
Insulin-like growth factors
Kinases
Ligands
Medical prognosis
Metastasis
Mice
Molecular Targeted Therapy
Mutation
Neoplasms - drug therapy
Neoplasms - metabolism
ophthalmopathy
Prostate cancer
Proteins
Psoriasis
Rats
Receptor, IGF Type 1 - antagonists & inhibitors
Review
Signal transduction
Signal Transduction - drug effects
Skin diseases
Skin Diseases - drug therapy
Skin Diseases - metabolism
Somatomedins - antagonists & inhibitors
Therapeutic targets
Thyroid
Tumors
type 1 IGF receptor
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Title Therapeutic Targeting of the IGF Axis
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