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

Shanmugasundara Ganapathy, Jean Francois H Geschwind

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number152
JournalMolecular Cancer
Volume12
Issue number1
DOIs
StatePublished - Dec 3 2013

Fingerprint

Glycolysis
Neoplasms
Therapeutics
Adenosine Triphosphate
Glucose
Oxidative Phosphorylation
Dermatoglyphics
Pyruvic Acid
Energy Metabolism
Lactic Acid
Oxygen
Phenotype
Food

Keywords

  • Antiglycolytic agents
  • Cancer metabolism
  • Chemotherapy
  • Glycolysis

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Tumor glycolysis as a target for cancer therapy : Progress and prospects. / Ganapathy, Shanmugasundara; Geschwind, Jean Francois H.

In: Molecular Cancer, Vol. 12, No. 1, 152, 03.12.2013.

Research output: Contribution to journalArticle

@article{5235e4a3669b41fb82593c196f2b1aae,
title = "Tumor glycolysis as a target for cancer therapy: Progress and prospects",
abstract = "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.",
keywords = "Antiglycolytic agents, Cancer metabolism, Chemotherapy, Glycolysis",
author = "Shanmugasundara Ganapathy and Geschwind, {Jean Francois H}",
year = "2013",
month = "12",
day = "3",
doi = "10.1186/1476-4598-12-152",
language = "English (US)",
volume = "12",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Tumor glycolysis as a target for cancer therapy

T2 - Progress and prospects

AU - Ganapathy, Shanmugasundara

AU - Geschwind, Jean Francois H

PY - 2013/12/3

Y1 - 2013/12/3

N2 - 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.

AB - 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.

KW - Antiglycolytic agents

KW - Cancer metabolism

KW - Chemotherapy

KW - Glycolysis

UR - http://www.scopus.com/inward/record.url?scp=84888798201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888798201&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-12-152

DO - 10.1186/1476-4598-12-152

M3 - Article

C2 - 24298908

AN - SCOPUS:84888798201

VL - 12

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

IS - 1

M1 - 152

ER -