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There have been many new developments in the field of cancer gene therapy since my previous articles on January 30 and February 6 of this year. I thought it appropriate, therefore, to provide you with this update. As you will recall, gene therapy involves the transfer of genes into cells in order to correct or disrupt a pathologic process.
A major problem with the use of cancer gene therapy occurs if each cancer cell must receive the gene product at the time of treatment. In these cases, cancer cells not so treated may be free to grow and metastasize. The treatment can be much more effective if the therapeutic agent can spread to neighboring cells and kill them as well. The understanding and application of this "bystander effect" is now important for gene therapy. Infecting tumor cells selectively The development of viruses that selectively infect only cancer cells are at the forefront of cancer therapy. 1How is this done? Scientists search for differences in gene and enzyme activity between normal and cancer cells, and capitalize on these differences to engineer viruses that only divide in the cancer cells. An example of this approach is the preparation of a herpesvirus that lacks the genes encoding the enzyme ribonucleotide reductase as well as a virulence gene. As a result, the virus can multiply efficiently only in dividing cells (cancer cells), and the lack of the virulence gene provides further safety against the spread of the infection to normal cells. This virus is currently completing Phase 1 clinical trials against malignant glial-cell tumors, a common type of brain tumor that is exceedingly difficult to treat. Another genetically engineered herpesvirus is undergoing early clinical trials against metastic melanoma. This is skin cancer that has spread, and is very difficult to successfully treat. Other workers have made a virus that selectively infects colon cancer cells. They realized that practically all colon cancer cells have a defect in a metabolic pathway that results in the accumulation of the molecules, beta-catenin and TCF-4. By engineering a virus that depends upon high levels of these molecules, the virus selectively multiplies in the colon cancer cells. Approaches based on the p53 tumor suppressor gene P53 is one of the most well known of the tumor suppressor genes, and is the focus of intense research effort, since about one-half of all cancers show defects in this gene. Normally, p53 protects against cancer, but when this gene becomes defective, it can turn into an oncogene and promote cancer instead. Introgen Therapeutics and Aventis Pharmaceuticals are collaborating in the development of a modified adenovirus that delivers p53 to lung and head and neck cancer cells. Phase II and II clinical trials are in progress, and the results so far indicate dramatic improvements in patient responses compared with traditional radiotherapy. Go To Page: 1 2
The copyright of the article New Developments in Gene Therapy in Cancer Treatment is owned by . Permission to republish New Developments in Gene Therapy in print or online must be granted by the author in writing.
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