Tumor aerobic glycolysis: new insights into therapeutic strategies with targeted delivery.
BACKGROUND
Cancer cells acclimatize to the harsh tumor microenvironment by altering cellular metabolism in favor of aerobic glycolysis. This process provides a source of energy and also generates essential components for macromolecular biosynthesis, which enables cellular survival. As the dependence of cancer cells on glycolysis affects tumorigenesis, it has become an attractive target for therapeutic intervention. Several preclinical studies have shown the effectiveness of using biological targets from the glycolytic pathway for anticancer therapy.


METHODS
This review provides an insight into the glycolytic pathway, highlighting potential targets for glycolytic inhibition. We then discuss recent advancement in delivery strategies that have the potential to circumvent some of the problems posed by current glycolytic inhibitors, enabling resurrection of abandoned therapeutic agents.


CONCLUSIONS
Targeting the glycolysis pathway is a tactical approach for cancer therapy. However, the current nonspecific therapeutic strategies have several drawbacks such as poor bioavailability, unfavorable pharmacokinetic profile and associated nonspecific toxicity, thereby limiting preclinical investigation. In recent years, nanoparticle systems have received recognition for the delivery of therapeutic agents directly to the tumor tissue. Thus, it is envisaged that this strategy can be expanded for the delivery of current glycolytic inhibitors specifically to tumor tissues providing improved anticancer activity.
Northeastern University, Pharmaceutical Sciences , 360 Huntington Avenue, 140 The Fenway Building, Boston, MA 02115 , USA.
Meghna
M
Talekar
Srinivas Reddy
SR
Boreddy
Amit
A
Singh
Mansoor
M
Amiji
D000332:Aerobiosis; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D019069:Cell Respiration / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents
aerobic glycolysis; glycolytic inhibitors; hypoxia; nanoparticles; targeted delivery