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September 2001. Review Article.
In oncology, gene therapy can be defined as the introduction of DNA into cells (either neoplastic or normal) in order to shrink or eliminate a malignant tumour. This may be achieved by means of inducing malignant cell death directly, by modulation of the immune response to tumours or by reversing the malignant process by correcting genetic abnormalities. It may also possible to enhance a tumour's responsiveness to conventional treatment such as chemotherapy and radiotherapy, and to protect normal tissue by introduction of genetic material that confers resistance to the toxic effects of such treatment.
One of the major problems in gene theraphy is difficulty in delivering the appropriate nucleic acid sequences to the target cells, and various strategies have evolved. Essentially these can be divided into those using viruses and those employing non viral vectors. The main viruses which have been studied as potential vectors for transducing genes into cancer cells are retroviruses and adenoviruses. The most widely studied non-viral vector is the liposome. Another approach is to use direct injection of plasmid DNA, but this technique can only transfect cells immediately adjacent to the injection site so that only a small number of cells can be treated.
Aside from different approaches to introducing genetic material into cells, gene therapy can be classified according to the different end results. The main aims in this respect are gene replacement (it involves the treatment of a tumour with a defective tumour suppressor gene by the transfer of a normal or super-active version of the gene ), antisense therapy ( when oligonucleotides bind to the complementary RNA or DNA they prevent translation or transcription, respectively), cytotoxic gene therapy ( the transduction of a tumour cells with a gene which leads to the production of an enzyme that can intracellularly convert a non-toxic compound or "prodrug" into an effective cytotoxic agent), immunotherapy (it improves the host's immune response to a particular tumour), and drug resistance transfer.
For more information about ongoing gene therapy trials for gastric cancer and phase 1 studies: http://www.wiley.co.uk/genetherapy.
Gene therapy for gastric cancer is on horizon. The main problems to overcome will be optimising delivery in order to maximise the proportion of cancer cells successfully transduced and choosing the most appropriate target for an individual tumour.
RJC Steele, DP Lane. Gene therapy for gastric cancer: problems and prospects. Surgical Oncology 9 (2000), 13-16.
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