Gene Therapy Produces Survival Benefit in Select Patients with Advanced Ovarian
Every human being inherits their traits from their parents. Genes are chemical molecules that are responsible for transferring these traits from parents to offspring. Genes contain all of the information needed by every cell in the human body for maintenance and growth. Cancer often develops when an abnormal alteration in a gene sequence occurs, causing normal cells in the body to become cancerous. In addition, gene alterations may disable the immune system, thereby preventing it from destroying cancer cells in the body. Gene therapy involves manipulation of genes in order to correct or override the abnormal alterations that cause cancer. This can be accomplished by replacing or inactivating a dysfunctional gene, replacing or inserting a functional gene.
Ovarian cancer is a common malignancy occurring in women in the United States with about 25,000 new cases diagnosed each year. The ovary makes female hormones and stores all the eggs that are released once a month during ovulation. There are two ovaries, one on each side of the uterus. The earlier ovarian cancer is detected, the higher the cure rate. Unfortunately, because ovarian cancer begins deep in the pelvis and often does not cause any symptoms until advanced stages, the disease often goes unnoticed until it has reached a stage where it is incurable. Most women with ovarian cancer have advanced disease at the time of diagnosis. This means the cancer has spread from the ovary to other body locations within the abdomen, such as the surface or inside of the liver, intestine, or lymph nodes.
Many different types of cancers develop due to a mutation (alteration) in a certain gene called the p53 gene. This gene, sometimes called the “cell suicide” gene, keeps normal cell replication under strict control. If there is an abnormality in a cell, the p53 gene normally stops replication of this damaged cell, inhibiting further progression of any detrimental abnormality. However, in cells that have a mutation within their p53 gene, there is no restraint on abnormal replication, leading to uncontrolled, rapid growth of the cells – the hallmark trait of cancer.
Early clinical trials involved a genetically manipulated virus that was developed to carry a normal p53 gene within itself. The virus was “programmed” to insert a normal copy of the p53 gene inside cells with a mutated p53 gene. Therefore, if a patient has cancer that has developed due to a mutated p53 gene, the cancer may be treated by inserting a normal p53 gene in to the cancer cell. The normal p53 gene causes the cancer cell to kill itself.
Researchers from the University of Iowa have reported that using gene therapy in select patients with advanced ovarian cancer may significantly improve survival. These promising results are derived from early phase clinical trials, and additional clinical trials are currently underway to determine the role of gene therapy in clinical practice.
In a recent clinical trial, 36 patients with advanced ovarian cancer received gene therapy treatment involving a manipulated virus to deliver a functional p53 gene. All of the patients had received multiple courses of standard treatment prior to these clinical trials.
Patients in the trial received multiple courses of gene therapy in combination with chemotherapy. Almost half of the patients who received gene therapy showed a significant regression of their cancer. One-quarter of the patients were still alive almost 20 months following treatment. This appears to be a significant improvement in survival over standard therapies for patients with advanced recurrent ovarian cancer. Future clinical trials will be conducted to directly compare this gene therapy strategy to current standard treatments for ovarian cancer in order to further define treatment outcomes.
Since patients with advanced ovarian cancer are typically considered incurable, these results are extremely encouraging as they show hope for the development of new treatment strategies for this deadly disease. Patients with ovarian cancer may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating this gene therapy approach or other promising treatment strategies. (
Proceedings from the Fourth Annual Gene Therapy and Molecular Biology Conference, 2000)
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