Tumor glycolysis as a target for cancer therapy: progress and prospects

Molecular Cancer

Review

Shanmugasundaram Ganapathy-Kanniappan¹  Jean-Francois H Geschwind² 

[1] Russell H Morgan Department of Radiology & Radiological Sciences, Division of Interventional Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock Building 340, 21287, Baltimore, MD, USA;Russell H Morgan Department of Radiology & Radiological Sciences, Division of Interventional Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock Building 340, 21287, Baltimore, MD, USA;Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Vascular and Interventional Radiology, Sheikh Zayed Tower, Suite 7203, The Johns Hopkins Hospital, 1800 Orleans Street, 21287, Baltimore, MD, USA;

关键词: Glycolysis;    Antiglycolytic agents;    Cancer metabolism;    Chemotherapy;   

DOI  :  10.1186/1476-4598-12-152

 received in 2013-07-29, accepted in 2013-11-21,  发布年份 2013

来源: Springer

【 摘 要 】

Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the “hallmarks of cancer”. This metabolic phenotype is characterized by preferential dependence on glycolysis (the process of conversion of glucose into pyruvate followed by lactate production) for energy production in an oxygen-independent manner. Although glycolysis is less efficient than oxidative phosphorylation in the net yield of adenosine triphosphate (ATP), cancer cells adapt to this mathematical disadvantage by increased glucose up-take, which in turn facilitates a higher rate of glycolysis. Apart from providing cellular energy, the metabolic intermediates of glycolysis also play a pivotal role in macromolecular biosynthesis, thus conferring selective advantage to cancer cells under diminished nutrient supply. Accumulating data also indicate that intracellular ATP is a critical determinant of chemoresistance. Under hypoxic conditions where glycolysis remains the predominant energy producing pathway sensitizing cancer cells would require intracellular depletion of ATP by inhibition of glycolysis. Together, the oncogenic regulation of glycolysis and multifaceted roles of glycolytic components underscore the biological significance of tumor glycolysis. Thus targeting glycolysis remains attractive for therapeutic intervention. Several preclinical investigations have indeed demonstrated the effectiveness of this therapeutic approach thereby supporting its scientific rationale. Recent reviews have provided a wealth of information on the biochemical targets of glycolysis and their inhibitors. The objective of this review is to present the most recent research on the cancer-specific role of glycolytic enzymes including their non-glycolytic functions in order to explore the potential for therapeutic opportunities. Further, we discuss the translational potential of emerging drug candidates in light of technical advances in treatment modalities such as image-guided targeted delivery of cancer therapeutics.

【 授权许可】

CC BY   
© Ganapathy-Kanniappan and Geschwind; licensee BioMed Central Ltd. 2013