Defining the pathway to insulin-like growth factor system targeting in cancer

The insulin-like growth factors (IGFs; IGF-1 and IGF-2) play central roles in cell growth, differentiation, survival, transformation and metastasis. The biologic effects of the IGFs are mediated by the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase with homology to the insulin receptor (IR). Dy...

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Bibliographic Details
Published in:Biochemical pharmacology 2010-10, Vol.80 (8), p.1115-1124
Main Authors: Rosenzweig, Steven A., Atreya, Hanudatta S.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Biological and medical sciences
Drug Delivery Systems
Humans
IGF-1 receptor
Insulin-Like Growth Factor Binding Proteins
Medical sciences
Neoplasms - drug therapy
Pharmacology. Drug treatments
Receptor tyrosine kinase
Receptor, IGF Type 1 - antagonists & inhibitors
Resistance
Somatomedins - metabolism
Targeted therapeutics
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Summary:The insulin-like growth factors (IGFs; IGF-1 and IGF-2) play central roles in cell growth, differentiation, survival, transformation and metastasis. The biologic effects of the IGFs are mediated by the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase with homology to the insulin receptor (IR). Dysregulation of the IGF system is well recognized as a key contributor to the progression of multiple cancers, with IGF-1R activation increasing the tumorigenic potential of breast, prostate, lung, colon and head and neck squamous cell carcinoma (HNSCC). Despite this relationship, targeting the IGF-1R has only recently undergone development as a molecular cancer therapeutic. As it has taken hold, we are witnessing a robust increase and interest in targeting the inhibition of IGF-1R signaling. This is accentuated by the list of over 30 drugs, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) that are under evaluation as single agents or in combination therapies [1]. The IGF-binding proteins (IGFBPs) represent the third component of the IGF system consisting of a class of six soluble secretory proteins. They represent a unique class of naturally occurring IGF-antagonists that bind to and sequester IGF-1 and IGF-2, inhibiting their access to the IGF-1R. Due to their dual targeting of the IGFs without affecting insulin action, the IGFBPs are an untapped “third” class of IGF-1R inhibitors. In this commentary, we highlight some of the significant aspects of and prospects for targeting the IGF-1R and describe what the future may hold.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2010.06.013