Colorectal carcinoma (CRC) remains a significant medical challenge with an expected 350000 new cases per year. Although the primary cancer can be successfully controlled by surgical resection, metastatic disease to the liver is the most common demise of the CRC patient. New innovative approaches must be developed for the treatment of CRC hepatic metastasis if the overall 2- and 5-year survival rates and quality of life assessments are to improved. We now describe an innovative gene therapy approach for the treatment of metastatic CRC, an approach called VDEPT. In this approach, an artificial chimeric gene is created which consists of two components: (1) the transcriptional regulatory sequence (TRS) of the human carcinoembryonic antigen gene (CEA); and (2) the protein coding domain of the nonmammlian cytosine deaminase gene (CD). This artificial gene will express CD only in cells which naturally express CEA. Expression of CD in CEA-positive cells is, by itself, nontoxic. However, CD can convert the nontoxic prodrug, 5-fluorocytosine (5-FCyt), to the toxic anabolite, 5-fluorouracil (5-FUra). Hence, the toxic compound, 5-FUra, will be selectively produced in cells which express CD. Since expression of CD is restricted to CEA-positive cells, 5-FUra will be selectively produced in CEA-positive cells. Hence, tumor-specific expression of CD permits the tumor-specific production of 5-FUra at high concentrations for extended periods of time directly at the tumor site. The artificial, chimeric gene can be delivered to CEA-positive tumors via a replication-defective retroviral vector. Chimeric genes composed of the human CEA promoter and the coding sequence of CD were created and engineered into a retroviral gene delivery vector. These chimeric genes selectively expressed CD in CEA-positive cells which resulted in the selective conversion of 5-FCyt to 5-FUra in the CEA-positive tumor cells. Human tumor xenografts demonstrated that expression of CD in solid tumors can generate complete cures if only 4% of the solid tumor cell mass expressed this enzyme. In vivo gene transfer has indicated that retroviral vectors can delivery and express CD chimeric genes in liver tumors at this 4% level.