Cytosine deaminase–uracil phosphoribosyltransferase enzyme system (CD–UPRT)

The cytosine deaminase–uracil phosphoribosyltransferase enzyme system comprises two distinct enzymes (CD and UPRT) sourced from either bacterial or yeast origins. In gene-directed enzyme prodrug therapy (GDEPT), tumor cells are genetically engineered to express these enzymes, enabling them to metabolize the non-toxic prodrug 5-fluorocytosine to toxic 5-fluorouracil and its active metabolites. This conversion drives selective tumor cell death and can induce a strong bystander effect due to the diffusion of toxic metabolites within the tumor microenvironment. Use of both enzymes together (CD–UPRT) offers greater efficacy and overcomes resistance mechanisms limiting 5-FU toxicity, and has shown promising results in preclinical cancer models[1][2][3].

Other names

Cytosine deaminase (CD)Uracil phosphoribosyltransferase (UPRT)CD–UPRT fusion proteinYCD–YUPRT (for yeast enzyme variants)E. coli CD–UPRT (for bacterial enzyme variants)

Cytosine deaminase converts 5-FC (non-toxic) into 5-FU (cytotoxic antimetabolite)[2][3]. UPRT rapidly converts 5-FU into 5-fluorouridine monophosphate, increasing the generation of active nucleotides that inhibit thymidylate synthase and are incorporated into RNA/DNA, leading to inhibition of DNA/RNA synthesis and cell death[2][3]. The system enables **bystander cytotoxicity**, as toxic metabolites can diffuse to neighboring cells[2].