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A Study of the Synergistic Activity of Cdk5 and TGF-Β Inhibitors in Pediatric Solid Tumors.

AJAS · 2018 Biomedical and Health Sciences (inferred)

Anish Ganesh · Chagrin Falls

Overview

On average, 15,780 cases of pediatric cancer are diagnosed within the United States annually. Furthermore, pediatric solid tumors account for about 30 percent of all cases of pediatric cancer (Cancer in Children, 2014). Previous studies on pediatric cancer have shown high expression of the two proteins Cyclin-dependent kinase 5 (Cdk5) and Transforming Growth Factor beta (TGF-Beta) (Chen, 2015). Cdk5 is an enzyme that was first shown to play a key role in the development of neuronal cells via phosphorylation of substrate proteins. TGF-Beta is a cytokine that signals and regulates cancer cell growth and tumor development by influencing cell function in the tumor microenvironment. Cdk5 inhibition suppresses cancer cell growth, but these effects are complicated by the emergence of resistance to inhibition. The hypothesis is that simultaneous exposure to inhibitors of Cdk5 and of the TGF-Beta receptor kinase TbRI will synergistically suppress the growth of pediatric solid tumors. Combinations of Cdk5 and TGF-Beta inhibitors were analyzed independently to establish dose response curves, and were analyzed together. Suppression was measured by the percentage of cell confluency using the Incucyte ZOOM®. There was a 35.62 percent decrease in confluency in the presence of both inhibitors relative to the control, while exposure to Cdk5 and TGF-Beta inhibitors alone was associate with only a 22.65 and 4.16 percent decrease, respectively. Thus, TGF-Beta and Cdk5 inhibitors acted synergistically to decrease proliferation in pediatric solid tumors in vitro. Future studies will focus on time and dose-dependent responses in to inhibitors of TGF-Beta and Cdk5 in a broader subset of pediatric cancers.

Competition history

  • AJAS 2018 Category not listed

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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science

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