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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells8080895