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Insulin-like growth factor system in cancer: novel targeted therapies.

Brahmkhatri VP, Prasanna C, Atreya HS - Biomed Res Int (2015)

Bottom Line: These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs).We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions.This can lead to the development of novel cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: NMR Research Centre, Indian Institute of Science, Bangalore 560012, India.

ABSTRACT
Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies.

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Related in: MedlinePlus

Structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 represented as CBP-1 (1ZT5), CBP-2 (2H7T), and CBP-6 (1RMJ), respectively.
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fig5: Structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 represented as CBP-1 (1ZT5), CBP-2 (2H7T), and CBP-6 (1RMJ), respectively.

Mentions: The structural features of IGFBPs, which carry IGFs in the circulation, are very important for understanding their role in normal growth and development as well as in diseases. The insulin-like growth factor binding protein-2, the second most abundant IGFBP in circulation and known to form binary complexes with IGF, is 32‚ÄČkDa (289 amino acid residues) in size with three distinct regions: the highly conserved N-terminal region (IGFBP homolog domain), the highly conserved C-terminal region with thyroglobulin type 1 repeat [95], and the mid-region known as the linker domain of IGFBP-2 with multiple cleavage sites. The structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 are shown in Figure 5.


Insulin-like growth factor system in cancer: novel targeted therapies.

Brahmkhatri VP, Prasanna C, Atreya HS - Biomed Res Int (2015)

Structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 represented as CBP-1 (1ZT5), CBP-2 (2H7T), and CBP-6 (1RMJ), respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383470&req=5

fig5: Structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 represented as CBP-1 (1ZT5), CBP-2 (2H7T), and CBP-6 (1RMJ), respectively.
Mentions: The structural features of IGFBPs, which carry IGFs in the circulation, are very important for understanding their role in normal growth and development as well as in diseases. The insulin-like growth factor binding protein-2, the second most abundant IGFBP in circulation and known to form binary complexes with IGF, is 32‚ÄČkDa (289 amino acid residues) in size with three distinct regions: the highly conserved N-terminal region (IGFBP homolog domain), the highly conserved C-terminal region with thyroglobulin type 1 repeat [95], and the mid-region known as the linker domain of IGFBP-2 with multiple cleavage sites. The structures of C-terminal domains of IGFBP-1, IGFBP-2, and IGFBP-6 are shown in Figure 5.

Bottom Line: These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs).We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions.This can lead to the development of novel cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: NMR Research Centre, Indian Institute of Science, Bangalore 560012, India.

ABSTRACT
Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies.

Show MeSH
Related in: MedlinePlus