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Expert Opin Investig Drugs. 2008 Oct;17(10):1533-45. doi: 10.1517/13543784.17.10.1533 .

Glycolytic enzyme inhibitors in cancer treatment.

Author information

1
Catholic University, Department of Laboratory Medicine, Largo A. Gemelli 8, 00168 Rome, Italy. r.scatena@rm.unicatt.it

Abstract

BACKGROUND:

The radio- and chemotherapeutics currently used for the treatment of cancer are widely known to be characterized by a low therapeutic index. An interesting approach to overcoming some of the limits of these techniques is the exploitation of the so-called Warburg effect, which typically characterizes neoplastic cells. Interestingly, this feature has already been utilized with good results, but only for diagnostic purposes (PET and SPECT). From a pharmacological point of view, drugs able to perturb cancer cell metabolism, specifically at the level of glycolysis, may display interesting therapeutic activities in cancer.

OBJECTIVE:

The pharmacological actions of these glycolytic enzyme inhibitors, based primarily on ATP depletion, could include: i) amelioration of drug selectivity by exploiting the particular glycolysis addiction of cancer cell; ii) inhibition of energetic and anabolic processes; iii) reduction of hypoxia-linked cancer-cell resistance; iv) reduction of ATP-dependent multi-drug resistance; and v) cytotoxic synergism with conventional cancer treatments.

CONCLUSION:

Several glycolytic inhibitors are currently in preclinical and clinical development. Their clinical value as anticancer agents, above all in terms of therapeutic index, strictly depends on a careful reevaluation of the pathophyiological role of the unique metabolism of cancer cells in general and of Warburg effect in particular.

PMID:
18808312
DOI:
10.1517/13543784.17.10.1533
[Indexed for MEDLINE]

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