Tumor glycolysis as a target for cancer therapy: progress and prospects
By Shanmugasundaram Ganapathy-Kanniappan, J. Geschwind. Molecular Cancer, 2013
1,224 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/006991da27065a928f7e30b96fdecd5f201b3fe0
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Citations in the corpus
- Drug resistance and combating drug resistance in cancer (2019, background): “For all the reasons mentioned above, inhibitors targeting glycolysis related proteins (GAPDH and LDH) like 3-bromopyruvate, oxamate and FX11 that significantly deplete intracellular ATP levels might sensitize cancer cells to anticancer drugs([170-174]).”
- Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory (2016, background): “The mutations of oncogenes in the up-regulation of glucose transporters increase the consumption of glucose by cancer cells, increasing the rate of glucose metabolism [41, 42].”
- 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs (2018, background): “…Siebeneicher et al. (2016) Silybin Clinical Phase I Baltazar et al. (2014), Siebeneicher et al. (2016) WZB117 Preclinical Ganapathy‐Kanniappan and Geschwind (2013) Hexokinase 2‐Deoxyglucose Clinical Phase IV Baltazar et al. (2014), Pelicano, Martin, Xu, and Huang (2006), Qian et al. (2014),…”