Gene therapy is based on the understanding that all cancers are due to malfunctioning genes. The defective or mutated genes may have a hereditary basis, but their expression depends upon environmental influences. The reasoning is that if the malfunctioning gene could be replaced with a normal functioning gene, the affected cells would no longer turn cancerous.
Recall that genes are located on chromosomes that are found in the nuclei of cells. Genes encode information that direct the synthesis of proteins that perform a wide variety of functions in the body. The traditional approach to treatment of disease is to develop drugs that combine with an abnormal protein that is causing the detrimental effect in the body. Due to the complexity of proteins, however, it may be simpler to develop treatments at the level of genes. Also, by treating at the level of genes, the body will be able to better control the formation and physiological action of the protein. In short, this approach should provide treatment that is more natural to body functioning with less detrimental side effects.
There are two broad categories by which malfunctioning genes can cause cancer: a)activation of oncogenes, and b)disactivation of tumor suppressor genes. The normal counterpart to oncogenes are the proto-oncogenes, which stimulate cell growth and division when they receive a signal to become active. When they are converted to oncogenes, they are continuously stimulated without the need for an external signal.Tumor suppressor genes are responsible for monitoring the genes on DNA for defects. If defects are found, the tumor suppressor genes initiate steps to correct the defects, or if correction is not possible, to command the cell to commit suicide through a process known as apoptosis. If a tumor suppressor gene is disactivated, a defective gene could become functional to the detriment of the cell.
In addition to correcting genes normally present in the cell's DNA, a very active area of research involves inserting genes into the cancer cell that make it produce a product that is eventually lethal to the cell.
The successful application of cancer gene therapy requires the following: (a) a vehicle must be found that will selectively deliver the genes to cancer cells but not healthy cells, (b) the gene (called the transgene) must be incorporated into the cell's DNA, (c) the transgene must become active and produce the product (hormone, enzyme, etc.) that it encodes for, and (d) the transgene must remain active. The major obstacle in the development of effective gene therapy is the use of the delivery vehicle, also called a vector.
