11.2 Gene Therapy of Cancer
11.2.1 Genetics of Cancer

Cell differentiation in eukaryote cell depends on the regulation of the cell division cycle. The cycle is controlled by a number of molecular factors.  Healthy cells grow, when there is a balance of stimulatory and inhibitory signals obtained from outside the cell that favor the cell proliferation. A cancerous cell does not respond to the usual signals and reproduces continuously forming more malignant cells. Cancer results from the uncontrolled proliferation of cells and from the ability of such cells to migrate to other sites (metastasis). There are many different causes of cancer, such as spontaneous genetic changes either by gene mutations or chromosome mutations.  The other are induced types, caused either by exposure to mutagens, radiation or cancer inducing viruses. Most cancers are considered of genetic disorders; i.e. they are caused by changes in DNA. Cancer results from genetic mutations that cause a loss in the ability of the cell to respond to regulatory signals, so the cell loses control on cell division. Mutant forms of gene involved in the regulation of the cell cycle are the cancer-causing genes.  The cell cycle is regulated at two sites, with two types of gene products these are, cyclins and kinases.

Recently, a number of genes related to the onset of cancer are identified. There are three classes of genes that have been shown to be mutated frequently in cancer.  These are oncogenes, tumour suppressor genes and mutator genes.  The products of oncogenes normally stimulate cell proliferation. Mutant oncogenes either are more active or become active inappropriately. The products of tumour suppressor genes normally inhibit cell proliferation.  Mutant tumour suppressor genes have lost their inhibitory function.

Oncogenes are genes that normally function to maintain cell division, these genes must be mutated or inactivated to stop cell division. If these genes become permanently switched on, cell division occurs in an uncontrolled way.  Proto-oncogenes normally function to promote cell division. These genes can be on or off. When they are on, they promote cell division. To stop cell division these genes must be inactivated. If these genes are permanently switched on then uncontrolled cell division occur, this leads to tumour formation. Therefore the mutant form of proto-oncogenes are known as oncogenes.

Tumour suppressor genes normally act to suppress cell division. If mutation occurs in these genes, cancer will appear.

Tumor viruses induce other types of cancer. Both DNA & RNA tumour viruses are known. DNA tumour viruses transform cells to the cancerous state through the action of a gene or genes that are essential parts of the viral genome. All RNA tumour viruses are retroviruses. These retroviruses contain cancer-inducing genes termed oncogenes. Both normal cells and non viral-induced cancer cells contain DNA sequences that are related to the viral oncogenes. It is found that the tumour causing retroviruses have picked up normal cellular genes called proto-oncogenes, while losing some of its own genetic information (Klug and Cummings 1997).