Abstract::
Enzyme prodrug therapy has gained momentum in the recent years due to their ability to improve therapeutic
index (benefits versus toxic side-effects) and efficacy of chemotherapy in cancer treatment. Inactive prodrugs used in this
system are converted into active anti-cancerous drugs by enzymes, specifically within the tumor cells. This therapy involves
three components namely prodrug, enzyme and gene delivery vector. Past reports have clearly indicated that the choice of
enzyme used, is the major determinant for the success of this therapy. Generally, enzymes from non-human sources are
employed to avoid off-target toxicity. Exogenous enzymes also give a better control to the clinician regarding the calibration
of treatment by site-specific initiation. Amongst these exo-enzymes, microbial enzymes are preferred due to their high
productivity, stability and ease of manipulation. The present review focuses on the commonly used microbial enzymes
particularly cytosine deaminase, nitroreductase, carboxypeptidase, purine nucleoside phosphorylase in prodrug activation
therapy. Various aspects viz. source of the enzymes, types of cancer targeted, mode of action and efficacy of the
enzyme/prodrug system, efficient vectors used and recent research developments of each of these enzymes are
comprehensively elaborated. Further, the results of the clinical trials and various strategies to improve their clinical
applicability are also discussed.
Cytosine Deaminase: A Pyrimidine Base Salvage Enzyme Vital to the Effectiveness of a Substrate Mediated Enzyme Prodrug Chemotherapy