Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)

Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)

This review focuses on the prodrugs used in suicide gene therapy. These prodrugs need to satisfy a number of criteria. They must be efficient and selective substrates for the activating enzyme, and be metabolized to potent cytotoxins preferably able to kill cells at all stages of the cell cycle. Both prodrugs and their activated species should have good distributive properties, so that the resu...

Isophosphoramide mustard analogues as prodrugs for anticancer gene-directed enzyme-prodrug therapy (GDEPT).

Two types of prodrugs, benzyl analogues of isophosphoramide mustard (iPAM), activated by cytochrome P450, and acylthioethyl analogues, activated by esterases, were designed. In contrast to iPAM that hydrolyse rapidly, the examined compounds are stable in phosphate-buffered saline and Tris buffer. Benzyl analogues of iPAM are poor substrates for cytochrome P450, are not cytotoxic and posses no a...

Cytochrome P450 gene-directed enzyme prodrug therapy (GDEPT) for cancer.

Several commonly used cancer chemotherapeutic prodrugs, including cyclophosphamide and ifosfamide, are metabolized in the liver by a cytochrome P450 (CYP)-catalyzed prodrug activation reaction that is required for therapeutic activity. Preclinical studies have shown that the chemosensitivity of tumors to these prodrugs can be dramatically increased by P450 gene transfer, which confers the capab...

Bystander or no bystander for gene directed enzyme prodrug therapy.

Gene directed enzyme prodrug therapy (GDEPT) of cancer aims to improve the selectivity of chemotherapy by gene transfer, thus enabling target cells to convert nontoxic prodrugs to cytotoxic drugs. A zone of cell kill around gene-modified cells due to transfer of toxic metabolites, known as the bystander effect, leads to tumour regression. Here we discuss the implications of either striving for ...

Prodrug-activating systems in suicide gene therapy.