Gene therapy of cancer.
The original concept of gene therapy was the introduction of a healthy copy of gene into an ill human cell in order to correct gene defects in monogenic hereditary diseases. Since then the idea of gene therapy was expanded to cure or slow down the progression of numerous inherited and acquired diseases. Presently, there are 918 ongoing gene therapy clinical trials worldwide. The major indication in these trials is cancer (608 trials or 66% of the total number). Gene therapy of cancer can be defined as transfer of nucleic acids into tumor or normal cells aiming at eradicating or reducing the tumor mass by direct killing of cells, immunomodulation or correction of genetic errors and reversion of the malignant status. Initially started with lots of optimism and enthusiasm, cancer genet therapy has shown limited success in the treatment of patients. This lesson highlights current limitations and almost endless possibilities of cancer gene therapy. The major difficulty in advancing gene therapy technology for the lab bench to clinical practice is the problem with gene delivery vehicles (so-called vectors) needed to ferry genetic material into a cell. Despite few reports of therapeutic responses in some patients, there is still no proof of clinical efficacy of most cancer gene therapy approaches, primarily due to very low transduction and expression efficacy in vivo of available vectors. An "ideal" gene therapy vector should: be administered through a noninvasive route; target not only the primary tumor mass but disseminated tumor cells and micrometastases at distant and unreachable sites as well; carry a therapeutic gene with tumor-restricted and time-regulated and sustained expression. Current strategies for combating cancer with gene therapy can be subdivided into 4 basic concepts: 1) replacement of missing tumor suppressor gene and/or blocking of oncogenes or proinflammatory genes; 2) suicide gene strategies; 3) induction of immune-mediated destruction; and 4) inhibition of tumor angiogenesis. Clinical advance will probably come first from cooperation with standard cancer treatment such as chemotherapy, radiotherapy and immunotherapy.
Mitrović
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Faculty of Sciences and Mathematics, Department of Biology and Ecology, Nis, Serbia and Montenegro.
Radulović
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