Suicide gene therapy safely inserts cancer-killing genes into tumor cells, causing those cells to self-destruct.[1] Suicide gene therapy is an emerging treatment for all types of cancer, including mesothelioma and lung cancer. Promising clinical trials could potentially lead to readily available treatment for most patients.
What Is Suicide Gene Therapy?
Suicide gene therapy is an evolving treatment that uses vectors like manipulated viruses to insert genes into cancer cells. The genes code for enzymes that activate drugs that kill the cancer cells.
About Gene Therapy
To understand this new type of treatment, it’s important to understand gene therapy in general.
Gene therapy is any treatment that manipulates genetic material. A gene is a sequence of nucleotides in DNA that provides a code for how a cell functions. Cancer cells have genes that prevent them from dying. This is why cancer cells grow and spread uncontrollably, causing disease.
Most types of gene therapy involve inserting the desired gene into a cell’s DNA. This is done through the use of a viral vector:
- A virus is inactivated so that it will not cause illness.
- Its DNA is manipulated to include a gene to be inserted into the DNA of a cancer cell or healthy cell.
- The virus is then injected into the patient, targets the correct cell, and inserts the gene.
- The result may be that the patient’s immune cells attack cancer cells.
- In the case of suicide gene therapy, cancer cells activate drugs that cause them to self-destruct.
How Does Suicide Gene Therapy Work?
Suicide gene therapy is related to chemotherapy, one of the most effective treatment strategies for mesothelioma. Chemotherapy uses toxic drugs that target cells that divide and grow rapidly. In most cases, the drugs are administered intravenously and circulate through the bloodstream.
These drugs are nonspecific, affecting both cancerous and healthy cells. As a result, healthy cells are commonly damaged, causing terrible side effects.
Suicide gene therapy specifically targets cancer cells with these toxic drugs but avoids 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 called an enzyme is inserted into the virus’s genetic material.[2]
- The patient 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, ganciclovir circulates in the body and is drawn into fast-growing cells. However, it does not harm healthy cells because the drug is not activated. Ganciclovir is a drug studied and used along with the herpes virus to treat cancers.
- The gene from the virus is inserted into the DNA of the cancer cells. When the prodrug reaches the cancer cells, the gene expresses a particular protein and activates the drug. The drug then kills the cancer cells. In other words, the newly inserted gene forces the cancer cells to “commit suicide.”
Suicide gene therapy provides a method of targeted activation for chemotherapy drugs to affect cancer cells without affecting healthy cells.
What Is The Bystander Effect in Suicide Gene Therapy?
A phenomenon known as the bystander effect helps increase the number of cancer cells that die during suicide gene therapy. The effect occurs when the gene from the herpes virus is inserted into one cell and affects surrounding cells, 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 in advancing suicide gene therapy.[3]
Is Suicide Gene Therapy an Effective Treatment for Mesothelioma?
Suicide gene therapy is being developed in clinical trials. It is not a type of treatment all patients can access, but the results from the trials are so far promising. Some patients with mesothelioma and lung cancer have benefited from the therapy.
One of the original studies of suicide gene therapy for mesothelioma occurred in the late 1990s. The researchers used a gene called HSV-tk, herpes simplex virus thymidine kinase, and a prodrug called ganciclovir. They successfully transferred the gene and found patients tolerated the treatment well.[4]
Animal studies have also proven the efficacy of this treatment strategy. Although trials do not demonstrate that suicide gene therapy is a cure for mesothelioma, it may extend a patient’s life without the serious side effects of chemotherapy.
What Is the Future of Suicide Gene Therapy? Challenges and Areas of Study
Suicide gene therapy presents some challenges. For example, transferring genes to the cancer cells is not foolproof and does not work for every patient. In fact, the efficiency of transferring the gene is low, and many patients never get the gene inserted into their cancer cells.
Although the bystander effect helps, it is not always enough. Other challenges include the possibility of side effects. While most patients experience only mild side effects, liver problems, skin disorders, inflammation, fevers, and anemia are possibilities.
As researchers continue to work on suicide gene therapy for mesothelioma and lung cancer, they must improve gene transfer efficiency while minimizing side effects.
A study using cell lines rather than patients found that using a gene called elongation factor 1-alpha (EF1A) along with HSV-tk improved the rate of gene transfer and increased the number of mesothelioma cells destroyed.[5] It could be used in patients in the future.
Research in suicide gene therapy began with HSV-tk, but other genes show promise. Researchers are considering using many other genes that could promote cell death in tumors.
Researchers may also combine suicide gene therapy with other treatments for greater effectiveness. Combining suicide gene therapy with treatments that boost the patient’s immune system could provide a two-pronged approach to cancer treatment. Combining this therapy with surgery or radiation may also increase effectiveness.
Gene therapy is an exciting area of research, especially for patients with diseases like mesothelioma. Gene manipulation is becoming easier, safer, and faster as technology improves. Suicide gene therapy provides amazing potential for new and effective treatments for all kinds of cancer, including mesothelioma and lung cancer. This emerging therapy offers hope for those living with cancer.
