Adenoviral gene therapy of gastrointestinal tumour metastases in the liver

Gastrointestinal cancers are the second most common cause of cancer death. Once metastasised, 5 year survival is < 5% in gastrointestinal cancer. Beca use the liver is the preferred site for distant organ metastasis of colon c ancer, treatment of hepatic metastases remains a challenge for experimental cancer therapy approaches. Gene therapy provides tools to combat cancer on a molecular level. In contrast to conventional chemotherapy, vectors are u sed to insert DNA into tumour cells, neighbouring parenchymal cells, or cel ls involved in the cellular immune defense. The shuttle vectors are of nonv iral or viral origin. Adenoviral vectors have been developed for high effic iency in vivo gene transfer and expression. The incorporation of foreign DN A can result in direct tumour cell killing, using suicide genes. Cytokine g enes, or genes encoding for tumour-specific antigens recognised by the cell ular host immune system, can result in antitumoral immune stimulation. Expe rimental suicide-gene expression in hepatic metastasis of gastrointestinal tumours, utilising thymidine kinase and cytosine deaminase, results in sign ificant tumour necrosis and regression. Intratumoral interleukin-2 and inte rleukin-12 gene expression can induce a systemic cellular antitumoral immun e response, with long-term survival demonstrating the potential of this new therapeutic approach in cancer therapy.