Current strategies in cancer gene therapy

Cancer gene therapy is the most studied application of gene therapy. Many genetic alterations are involved in the transformation of a normal cell into a neoplastic one. The two main gene groups involved in cancer development are oncogenes and tumor suppressor genes. While the latter eliminates cancerous cells via apoptosis, the former enhances cell proliferation. Therefore, apoptotic genes and anti-oncogenes are widely used in cancer gene therapy. In addition to oncogenes and tumor suppressor genes, chemotherapy and gene therapy can be combined through suicide gene strategy. A suicide gene encodes for a non-mammalian enzyme; this enzyme is used to convert a non-toxic prodrug into its active cytotoxic metabolite within the cancerous cells. Tumor suppressor genes, anti-oncogenes and suicide genes target cancer cells on the molecular level. On the other hand, cancer is immunogenic in nature; therefore, it can also be targeted on the immunological level. Boosting the immune response against cancerous cells is usually achieved via genes encoding for cytokines. Interleukin-12 gene, for example, is one of the most studied cytokine genes for cancer gene therapy applications. DNA vaccines are also used after conventional treatments to eliminate remnant malignant cells. All these therapeutic strategies and other strategies namely antiangiogenesis and drug resistant genes are briefly reviewed and highlighted in this article. (C) 2004 Elsevier B.V. All rights reserved.