NF-κB inhibitors in clinical management for Cancer and diabetes treatment: The IL-6 Potential

Abstract

The association between obesity and chronic inflammatory diseases such as type 2 diabetes (T2D) and several types of cancer can be seen as a result of obesity-induced low-grade inflammation. Enlarged adipose tissue in obesity results in the release of free fatty acids (FFAs) and inflammatory cytokines including IL-1β, IL-6 and tumour necrosis factor (TNF-α), which play a crucial role in the pathogenesis of diabetes and cancer development. Studies conducted in our lab have shown that FFAs increased the expression of Iκβ kinase (IKKβ) which promotes inflammation by acting on the NF-κB transduction cascade. Similar studies were reported in different research models. Inflammation-mediated cell death, fibrosis, and angiogenesis have been found to be caused by NF-κB activation, making NF-κB inhibitors promising targets in the treatment of cancer and diabetic complications. Recent investigations and supportive evidence have demonstrated that NF-κB antagonists are key players in the development and prevention of cancer, along with the management of vascular complications of diabetes. Mechanistically, these NF-κB inhibitors suppress the amplification of IL-6 by suppressing NF-κB-STAT3. It is intriguing to further elucidate the biomarkers linked mechanisms. The low grade inflammation mediators such as IL-1β, IL-6 and TNF-α were reported in diabetes and cancer. The current poster points out the importance of measuring the inflammatory biomarker, IL-6 as a surrogate screening marker in diabetes and cancer with a focus on increasing the efficacy of therapeutic strategies that can target various levels of NF-κB-STAT3-IL-6 signaling for treatment modalities.