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Suicide Gene Therapy

Gene therapy is a promising emerging line of treatment for mesothelioma and lung cancer, as well as other types of cancer. These therapies involve manipulating the genes in the DNA of patient’s cells, tumor cells, and even in viruses to attack and selectively kill the cancer cells in patient’s bodies. Sometimes the strategy is to boost the patient’s immune system, while in other cases the idea is to alter the cancer cell’s genes to make them more susceptible to treatment.

For mesothelioma and asbestos-related lung cancer, which are notoriously aggressive and difficult to treat, suicide gene therapy is a particularly promising line of gene therapy treatment. Researchers are working through clinical trials using gene modification to force cancer cells to self-destruct after being targeted with certain drugs. The results are promising and clinical trials will hopefully lead to readily available treatment for most patients.

What is Gene Therapy?

Gene therapy is any treatment that manipulates genetic material. Genes are the coded messages in the DNA at the control centers of all living cells. The genes code for proteins, which then go on to perform all the functions of the cell. In cancer cells there are genes that prevent them from dying, which is why they grow and spread uncontrollably, causing disease.

Most types of gene therapy involve inserting a desired gene into the DNA of a cell. This is done through the use of a viral vector. A virus is inactivated—it will not cause illness in this state—and its DNA is manipulated to include a gene that is to be inserted into the DNA of a cancer or healthy cell. The virus is then injected into the patient and it goes to the correct cell and inserts the gene. The result may be that the patient’s immune cells begin attacking cancer cells or in the case of suicide gene therapy, that cancer cells activate drugs that cause them to self-destruct.

What is Suicide Gene Therapy?

Suicide gene therapy is related to chemotherapy, one of the most effective strategies for treating mesothelioma. Chemotherapy is the administration of toxic drugs that kill rapidly growing and dividing cells. In most cases the drugs are administered intravenously, they circulate throughout the body in the bloodstream, and they attack and kill fast-growing cells, both cancerous and healthy. The result may be death to cancer cells, but the damage to healthy cells causes terrible side effects.

The underlying idea of suicide gene therapy is targeting cancer cells specifically with these toxic drugs, and avoiding damage to healthy cells. Targeted chemotherapy has been a major challenge in cancer treatment. Suicide gene therapy starts with a genetically-modified virus, most often the herpes simplex virus. The virus is first adapted so that it will not infect the patient with herpes, then a gene that codes for a special protein is inserted into the virus’s genetic material.

The patient being treated is then injected with the virus and a chemotherapy prodrug. A prodrug is an inactive form of a drug. Because it is inactive, it does not target and kill healthy cells. Like other chemotherapy drugs, it circulates in the body and is drawn into any fast-growing cells, but without being activated, it does no harm. The drug that has been studied and used along with the herpes virus to treat cancers is called ganciclovir.

The gene from the virus gets inserted into the DNA of the cancer cells. When the prodrug reaches the cancer cells, the gene expresses a special protein that activates it. The drug then does its job and kills the cancer cells. In other words, the newly inserted gene forces the cancer cells to “commit suicide.” Suicide gene therapy is a targeted way of activating chemotherapy drugs only in cancer cells, not healthy cells.

The Bystander Effect

A phenomenon known as the bystander effect helps to increase the number of cancer cells that die during suicide gene therapy. The effect occurs when the gene from the herpes virus is inserted to one cell and has an effect on the cells around it, even if those cells did not successfully receive the gene from the virus. Through means not entirely understood, the toxic drug is transported from one cell to another, causing the cells without the suicide gene to die as well. The bystander effect may play an important role going forward in the development of suicide gene therapy.

Suicide Gene Clinical Trials

This strategy for targeting cancer cells has been used in clinical trials with promising results. Some patients with mesothelioma or with lung cancer have benefitted from the therapy. Animal studies have also been used and have proven the effectiveness of the treatment. The trials are not demonstrating that suicide gene therapy is going to cure mesothelioma, but that it may extend a patient’s life without all the serious complications and side effects of systemic chemotherapy.

Suicide Gene Therapy Going Forward

There are challenges as the use of suicide gene therapy in clinical trials moves forward. One of these is the fact that the transfer of genes to the cancer cells is not foolproof. It does not always work in all patients. In fact, the efficiency of transferring the gene is still low and many patients never get the gene inserted into their cancer cells. The bystander effect helps, but may not be enough. Other challenges include the possibility of side effects. Most patients have not experienced any side effects, or only mild side effects. A few, however, experienced liver problems, skin disorders, inflammation, fevers, and anemia.

As researchers continue to work on suicide gene therapy for mesothelioma and lung cancer, they will need to improve the efficiency of gene transfer as well as minimizing side effects. They may also try combining suicide gene therapy with other treatments for greater effectiveness. One idea is to combine it with treatments that boost the patient’s immune system for a two-pronged attack on cancer cells. Combining this therapy with surgery or radiation may also be a treatment option.

Gene therapy is an exciting area of research, especially for patients living with terrible diseases like mesothelioma. Manipulating genes is getting easier, faster, and safer as technology improves and clinical trials continue to push the therapy further. With suicide gene therapy, there is great potential to develop new, better, and more effective treatments for all kinds of cancer, including mesothelioma and lung cancer. It is a type of therapy that gives hope to people living with cancer and their loved ones.

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