Tumor-Based p53 Therapy
Page Medically Reviewed and Edited by Anne Courtney, AOCNP, DNPThis page has been fact checked by a Doctor of Nursing Practice who specializes in Oncology and has experience working with mesothelioma patients.
Sources of information are listed at the bottom of the article. We make every attempt to keep our information accurate and up-to-date.
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Gene therapy is one of the hottest areas of research for many types of illnesses, including cancer. It is especially hopeful and promising for patients living with aggressive and incurable types of cancer, like mesothelioma or lung cancer caused by asbestos exposure. When other treatments have failed, or have caused painful side effects, gene therapy strategies may one day provide hope of a cure.
The strategy of gene therapy is to manipulate genes in the DNA of living cells to kill and conquer cancer cells. One type of gene therapy that has been especially promising for the treatment of lung cancer is based on p53, a gene that blocks tumor growth. The p53 therapy has been used successfully in clinical trials in China. The U.S. now has several options to test tumors for genetic mutations. Ongoing clinical trials are needed to determine the best treatment options for tumors with a p53 mutation.
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What Is Gene Therapy?
Gene therapy is a kind of treatment that involves the manipulation of genes in the DNA of living cells to treat or cure disease. DNA is the genetic material that is housed in the nucleus of all cells. It contains a coded message, with individual messages called genes. Each gene codes for the production of a protein. A cell makes proteins based on the genes in its DNA, and these proteins then carry out the functions of the cell.
Genes and their proteins are necessary for living cells and, therefore, all living organisms to grow, reproduce, and function. They can be faulty, though. When there is a mutation, or a change in genes, it can have disastrous consequences, including cancer. Asbestos, for instance, may cause mesothelioma by altering the genes in a person’s cells, resulting in out of control spread and growth.
Gene therapy manipulates genes to change the production of proteins and the actions of cells. In cancer treatment, this may involve inserting new genes. New genes can be placed in immune cells to make them attack cancer cells, or may be placed in cancer cells to cause them to self-destruct. Deactivated viruses are used to insert new genes into healthy cells and cancer cells.
The p53 Gene
One of the most important strategies in gene therapy involves the manipulation of a gene called p53. This gene is also often referred to as the guardian of the genome. p53 is a tumor suppressor gene. This means that it codes for a protein that stops the formation of tumors and the growth of cancer cells. Researchers have found that some people are predisposed to cancer because they inherit a working copy of this gene from one parent only, and referred to as a germline mutation. This is a rare condition and referred to as Li-fraumeni syndrome. More commonly, genetic mutations arise from the cancerous tumor itself, called somatic mutations. Having a somatic p53 mutation is common in most cancers.
The protein created by the p53 gene works by attaching and binding to DNA at a certain location. This stimulates the production of a second protein called p21. This protein then interacts with a protein that is related to cell division. The interaction prevents a cell from dividing and growing. This is important in preventing the uncontrollable division and growth seen in cancer cells that leads to the development of tumors. When the p53 gene is missing or inactivated, the p21 protein never gets made and cells don’t have their “stop sign”.
How p53 Gene Therapy Treats Cancer
Targeting the p53 gene has been a gene therapy strategy for a long time in gene therapy research, since it is so often implicated in cancer. The basic idea is to restore the function of the gene after something has gone wrong with it and caused cancer to develop. First, the mutated gene must be identified in the cancer cells, as not all cancers result from this p53 mutation. The aim of drugs would ideally restore the gene and allow it to return to the main function: to stop cancer cells from dividing.
The strategy for delivering a working copy of the gene is similar to that used for other gene therapies, including suicide gene therapy. A virus is used as a vector, or a carrier, to deliver a gene. The virus is first inactivated so that it will not make a patient sick. The desired gene, in this case p53, is then inserted into the virus’s DNA. The virus is injected into the patient’s cells and it transfers the p53 gene to the cells’ DNA. Viruses work so well in this role because they are already programmed to insert and attack cell segments of DNA, usually to cause infection, but in this case, to help kill cancer cells.
Clinical Trials and Use Outside the U.S.
The U.S. Food and Drug Administration has not yet approved any p53 gene therapy for the treatment of any cancer. It is the most common mutation found in cancer tumors. The therapy has been tested in clinical trials and has particularly shown great promise for treating lung cancer. Researchers continue to look at mutations found in several cancers to determine if there may be treatments that can be used on tumors with this mutation, regardless of where the cancer originally started.
Some clinical trials have used p53 gene therapy in combination with other types of treatment, including radiation. In one of these trials, the use of the gene therapy with radiation resulted in survival times four times longer than is normally achieved with just radiation therapy. In another clinical trial, some patients with lung cancer were effectively cured when the gene therapy was combined with chemotherapy and immunotherapy.
China has gotten much farther with the use of p53 gene therapy than the U.S. and has already approved it for widespread use in the treatment of certain types of cancer. This approval dates as far back as 2004 and China was the first country to approve gene therapy cancer treatments. Though much of the research into advancing p53 gene therapy is being conducted by Chinese researchers, American researchers and patients hope to benefit from it as well.
p53 Gene Therapy for Mesothelioma
So far there has not been a lot of research into the use of p53 gene therapy for the treatment of mesothelioma specifically, but asbestos lung cancer patients may soon benefit from it. The limited research into altering p53 to treat mesothelioma does show promise. The p53 pathway that leads to tumor growth is found to be abnormal in most cases of mesothelioma, and the injection of viral vectors for gene therapy into the chest cavity has been shown to be relatively safe for patients. More research will hopefully find effective ways to target p53 to treat pleural mesothelioma.
The advances in gene therapy to treat all types of cancer are truly astounding. New techniques and strategies are constantly being developed because technology that allows for the manipulation is advancing at such a fast pace. The targeting of p53 is expected to remain at the center of gene therapy because of the major role it plays in preventing, stopping, and when mutated, spreading tumors throughout the body. Patients with mesothelioma, and their loved ones, have hope for the future thanks to this research.
Page Medically Reviewed and Edited by Anne Courtney, AOCNP, DNP
Anne Courtney has a Doctor of Nursing Practice degree and is an Advanced Oncology Certified Nurse Practitioner. She has years of oncology experience working with patients with malignant mesothelioma, as well as other types of cancer. Dr. Courtney currently works at University of Texas LIVESTRONG Cancer Institutes.