Intra-peritoneal administration of genetic therapies: promises and pitfalls

Rapid advances in our understanding of the molecular basis of cancer development and progression over the past 3 decades have led to the design of new potential cancer therapies based on the expression of introduced genes into a tumor or its host. In an attempt to overcome the limitations of direct intratumoral administration of genetic therapies in patients with advanced malignant disease, loco-regional routes of delivery have been explored including the intraperitoneal route. This review highlights the potential of replication-competent oncolytic viruses, virus-mediated gene replacement, and gene-directed enzyme-prodrug strategies, as novel cancer therapies. The potential of exploiting the selectivity of the telomerase gene within cancer cells to develop gene therapy strategies is discussed and the promises and pitfalls in translating these novel therapeutics from the laboratory to the clinic are reviewed.