title: Enzyme/Prodrug Systems for Cancer Gene Therapy.
abstract: The use of enzyme/prodrug system has gained attention because it could help improve the efficacy and safety of conventional cancer chemotherapies. In this approach, cancer cells are first transfected with a gene that can express an enzyme with ability to convert a non-toxic prodrug into its active cytotoxic form. As a result, the activated prodrug could kill the transfected cancer cells. Despite the significant progress of different suicide gene therapy protocols in preclinical studies and early clinical trials, none has reached the clinic due to several shortcomings. These include slow prodrug-drug conversion rate, low transfection/transduction efficiency of the vectors and nonspecific toxicity/immunogenicity related to the delivery systems, plasmid DNA, enzymes and/or prodrugs. This mini review aims at providing an overview of the most widely used enzyme/prodrug systems with emphasis on reporting the results of the recent preclinical and clinical studies.
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States.
authors.forename: Obeid M
authors.initials: OM
authors.lastname: Malekshah
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nomani
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States.
authors.forename: Siddik
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, United States.
authors.forename: Arash
authors.initials: A
authors.lastname: Hatefi
keywords: CB1954; CPT-11; GDEPT; SN-38; bystander effect; cancer gene therapy; carboxyl esterase; cytosine daminase; enzyme prodrug; ganciclovir; nitroreductase; suicide gene therapy; thymidine kinase