Biomol Ther  
A New Perspective on the Heterogeneity of Cancer Glycolysis
Michael L. Neugent1, Justin Goodwin2,3, Ishwarya Sankaranarayanan1, Celal Emre Yetkin1, Meng-Hsiung Hsieh1 and Jung-whan Kim1,*
1Department of Biological Sciences, The University of Texas at Dallas, Richardson, Texas 75080,
2Yale School of Medicine, New Haven, Connecticut 06510,
3Yale Graduate School of Art and Science, New Haven, Connecticut 06511, USA
E-mail: jay.kim@utdallas.edu
Tel: +1-972-883-3502, Fax: +1-972-883-4551
Received: October 17, 2017; Revised: October 28, 2017; Accepted: November 1, 2017; Published online: December 7, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.
Keywords: Glycolysis, Heterogeneity, Tumor microenvironment, Stroma, Metabolism, Cancer


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