Challenges in modulating insulin receptor signalling as a therapeutic strategy for cancer

Indian Journal of Medical Research  Year : 2018 | Volume: 147 | Issue: 6 | Page: 530-532 | https://dx.doi.org/10.4103%2Fijmr.IJMR_732_18  

Priya Srinivas, Madhavan Radhakrishna Pillai

Abstract

In spite of dissimilitude in the aetiology of diabetes and cancer, there are several overlapping risk factors such as obesity, lack of physical activity and dietary routines which predispose diabetic patients to cancer. Furthermore, several molecular signalling cascades, especially the deregulated insulin/insulin-like growth factor (IGF) axis pathways, could be evidenced in both these disease conditions. Insulin and IGF can activate the insulin receptor (IR) and insulin-like growth factor receptor (IGF-R), which are expressed as homo/hetero-dimer receptor proteins on the cell membrane, leading to subsequent PI3K-AKT/MAPK signalling resulting in enhanced uptake of glucose into the cell through GLUT-4 for glycolysis. Uncontrolled activation of this signalling cascade results in enhanced proliferation of the cells. When glucose is available to the cells, the glycolytic enzymes would be activated. The association of the phosphorylated forms of glucokinase and BAD (Bcl2 antagonist of cell death) proteins triggers the glycolytic pathway and results in subsequent enhanced cell proliferation. It has been reported that inhibition of insulin/IGF, their receptors or inhibitors of glucose metabolism intermediates such as phospho-BAD, blocks the glycolytic pathway and activates apoptotic signalling, thereby resulting in cell death.

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