Towards gene therapy for colorectal liver metastases

Hepatic gene therapy may provide a new approach to treating hepatic malignancies. A promising strategy involves the infection of tumor and liver cells with replication-defective adenoviral vectors carrying suicide genes. The products of these genes convert prodrugs into cytotoxic derivates. In the transduced cells the subsequently administered prodrugs are thus activated and destroy replicating tumor cells, whereas the infected liver cells are thought to be unaffected because of their minimal proliferative activity. A major concern about this approach is that the suicide genes can theoretically enter the germline and other organs with high mitotic activity and as a consequence, cause their destruction. In vivo gene delivery should therefore be tissue-specific, and methods for targeted gene delivery are required. Targeting the colorectal liver metastases is pursued by combining the suicide gene principle and the surgical technique of isolated perfusion of the liver.