Restoring proper gene function
I indicated in the previous article that cancer is caused by mutations in genes that control the cell division cycle. Oncogenes are mutations that cause an excessive stimulation of the cell cycle, while mutations in tumor suppressor genes can result in a loss in function in controlling this excessive activity. A major target of gene therapy is the tumor suppressor gene, p53. It has been found that there is a mutation of the p53 gene in about 50% of all cancers. When the DNA of the cell is damaged, p53 protein begins to accumulate. If the DNA damage is not too severe, p53 directs the formation of another protein, p21, which blocks further progression of the cell cycle until the DNA can be repaired. If the DNA cannot be repaired, p53 directs the cell to commit suicide through a process called apoptosis. A clinical study now in progress involves the replacement of defective p53 in patients with lung cancer. A delivery vehicle was prepared by inserting the p53 gene into an adenovirus vector. The adenovirus was injected repeatedly into the patient’s tumors. The majority of the patients showed a stabilization of the disease but not a cure. One of the most promising approaches to control oncogene activity is using antisense drugs. I will discuss antisense in detail in another article, but for now I will simply say that the antisense oligonucleotide (section of DNA) is complimentary in structure to the oncogene. Consequently, the antisense oligonucleotide binds to the oncogene, preventing the formation of its protein product. The oncogene then becomes inactive, and cannot cause overstimulation of the cell cycle. Preliminary results indicate that, similar to p53 therapy, the cancer can be controlled, but it is difficult to effect a cure. As a rule, it appears that every cancer cell must receive the replacement gene in order to cure the cancer.
