Limits...
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.

Show MeSH

Related in: MedlinePlus

Targeting IGFBPs, a novel strategy in cancer therapeutics. The cancer therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Drawback of such approaches is the adverse side effects or toxicities due to its interference with the insulin pathway. The more efficacious alternatives, IGFBPs, as IGF-antagonist based cancer therapeutics also contribute to block the IGF-1R, mediated tumour progression. As IGFBPs do not bind insulin, they do not interfere with insulin-insulin receptor interactions.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4383470&req=5

fig8: Targeting IGFBPs, a novel strategy in cancer therapeutics. The cancer therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Drawback of such approaches is the adverse side effects or toxicities due to its interference with the insulin pathway. The more efficacious alternatives, IGFBPs, as IGF-antagonist based cancer therapeutics also contribute to block the IGF-1R, mediated tumour progression. As IGFBPs do not bind insulin, they do not interfere with insulin-insulin receptor interactions.

Mentions: It is now clear that the IGFBPs have many effects on cell death, via both IGF-dependent and IGF-independent actions. Although the mechanisms underlying these latter actions are only beginning to be understood, it is already clear that they may provide very specific strategies for fine-tuning therapeutic interventions. Current therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Potential drawback of such approaches is the resulting adverse side effects or toxicities due to its interference with the insulin pathway. As a more efficacious alternative, we propose that IGFBPs can be developed as IGF-antagonist based cancer therapeutics serving to block the IGF-1R mediated tumour progression (Figure 8). The IGFBPs do not bind insulin and thus do not interfere with insulin-insulin receptor interactions.


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

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

Targeting IGFBPs, a novel strategy in cancer therapeutics. The cancer therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Drawback of such approaches is the adverse side effects or toxicities due to its interference with the insulin pathway. The more efficacious alternatives, IGFBPs, as IGF-antagonist based cancer therapeutics also contribute to block the IGF-1R, mediated tumour progression. As IGFBPs do not bind insulin, they do not interfere with insulin-insulin receptor interactions.
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Targeting IGFBPs, a novel strategy in cancer therapeutics. The cancer therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Drawback of such approaches is the adverse side effects or toxicities due to its interference with the insulin pathway. The more efficacious alternatives, IGFBPs, as IGF-antagonist based cancer therapeutics also contribute to block the IGF-1R, mediated tumour progression. As IGFBPs do not bind insulin, they do not interfere with insulin-insulin receptor interactions.
Mentions: It is now clear that the IGFBPs have many effects on cell death, via both IGF-dependent and IGF-independent actions. Although the mechanisms underlying these latter actions are only beginning to be understood, it is already clear that they may provide very specific strategies for fine-tuning therapeutic interventions. Current therapeutics targeting the IGF-signalling pathway focus on blocking IGF-1R, directly, and/or its downstream effect. Potential drawback of such approaches is the resulting adverse side effects or toxicities due to its interference with the insulin pathway. As a more efficacious alternative, we propose that IGFBPs can be developed as IGF-antagonist based cancer therapeutics serving to block the IGF-1R mediated tumour progression (Figure 8). The IGFBPs do not bind insulin and thus do not interfere with insulin-insulin receptor interactions.

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