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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Veröffentlicht in:Cells (Basel, Switzerland) Jg. 8; H. 8; S. 895
Hauptverfasser: Osher, Eliot, Macaulay, Valentine M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 14.08.2019
MDPI
Schlagworte:
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
Online-Zugang:Volltext
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Zusammenfassung: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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ISSN:2073-4409
2073-4409
DOI:10.3390/cells8080895