Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis

Gene therapy is a novel therapeutic approach that might soon improve the pr ognosis of some cancers. We investigated the feasibility of cytosine deamin ase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/ K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene w ere highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect cou ld also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine trip hosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and t o prolonged survival. Our study thus demonstrated the efficacy of CD suicid e gene therapy for the treatment of peritoneal carcinomatosis.