Current Pharmaceutical Design - Volume 9, Issue 26, 2003

The problems associated with conventional anticancer agents that exert their actions by cytotoxicity are well known and often are dose limiting with regard to the therapeutic opportunity. Identification of strategies that rely on tumour selective drug activation is a very attractive approach to minimising host tissue toxicity and in principle can allow drug dosing regimens that are ultimately curative. Prodrug activation is central t Read More

CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] has been the subject of continued interest for over 30 years. As an anti-cancer agent, it represents one of the very few examples of a compound that shows real anti-tumor selectivity. Unfortunately, for the treatment of human disease, this anti-tumor selectivity was seen only in certain rat tumors. The basis for the anti-tumor selectivity of CB 1954 is that it is a prodrug that is enz Read More

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and / or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or Read More

Clinically useful prodrug activation systems for cancer therapy can be applied in combination with the exogenous activating enzymes, by which masked prodrugs are able to unmask to exert cytotoxic effects on the target tumors. In essence, designing prodrugs not to be degenerated or activated by the endogenous enzymes is needed. Prodrug activation systems are to be delivered to the tumor site by delivery tools, incl Read More

Improvements in the radiotherapeutic management of solid tumors through the concurrent use of gene therapy is a realistic possibility. Of the broad array of candidate genes that have been evaluated, those encoding prodrug-activating enzymes are particularly appealing since they directly complement ongoing clinical chemoradiation regimes. Gene- Directed Enzyme-Prodrug Therapy (GDEPT) only requires a fraction of the Read More

This review is a survey of two approaches for a selective anticancer therapy that are based on a specific cleavage of specially designed non-toxic prodrugs with the liberation of a cytotoxic compound either by antibody-enzyme conjugates targeted to tumor-associated antigens or by acid-catalyzed hydrolysis of the prodrugs due to the increased concentration of hydronium ions in malignant tissue under hyperglycemic con Read More