Can we consider cancer to be a "metabolic disease"? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have increased needs for both energy and biosynthetic intermediates to support their growth and invasiveness. However, their high proliferation rate often generates regions that are insufficiently oxygenated. Therefore, their carbohydrate metabolism must rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the Warburg effect, constitutes a fundamental adaptation of tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that antiglycolytic agents may cause serious side effects toward normal cells. The key to selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anticancer drugs with minimal toxicity. There is growing evidence to support many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant antiglycolytic agents that have been investigated thus far for the treatment of cancer.
|Autori:||C. GRANCHI; F. MINUTOLO|
|Titolo:||Anticancer Agents That Counteract Tumor Glycolysis|
|Anno del prodotto:||2012|
|Digital Object Identifier (DOI):||10.1002/cmdc.201200176|
|Appare nelle tipologie:||1.1 Articolo in rivista|