Evaluating the therapeutic effect of 2-Deoxy-D-glucose on various cancer models.

Authors

Nathan Labrie

Document Type

Article

Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory

Abstract

Cancer is one of the most pervasive diseases yet known and is accredited with over 8.8 million deaths in 2015 alone. Cancer, which is caused by mutations in the genome of an organism during cellular division, has no completely effective treatments. The Warburg effect which provides the necessary energy requirements for the unchecked growth exhibited by many tumorigenic models. In an effort to counter the advantages of the Warburg effect, this study focuses on the glycolytic inhibitor 2-Deoxy-D-glucose (2DG) as a possible treatment to minimize the proliferation of cancerous cells. Recent results from the Roopenian laboratory suggest the synergistic relationship between 2DG and tumorigenic cells could serve as a possible chemotherapeutic agent. Here we have tested the hypothesis that inhibiting glycolysis with 2DG is an effective chemotherapy for Chronic lymphocytic leukemia (Cll), Acute lymphocytic leukemia (All), lung Squamous Cell Carcinoma (lSCC) and spontaneous cancers. Various mouse models were utilized including Trp53 -/- and Patient Derived Xenograft (POX). Mice were developed to have a spontaneous tumor or given a tumor load and treated respectively with 2DG. We found that 2DG was most effective in cell types that favored glycolysis opposed to oxidative phosphorylation. The results of this study are expected to open a new avenue for chemotherapy research.

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