Suicide gene therapy is a promising method for destroying cancer cells without harming healthy ones. Two methods are currently used: enzyme-gene prodrug therapy and virus-directed enzyme-prodrug therapy. The therapy has already proven effective against prostate and bladder cancers and is being extended to other forms of cancer. A polymer is being explored as a safer alternative to using a virus as a delivery agent. The existence of a different type of suicide gene is also being explored as a possible explanation for higher incidences of suicide in some families.
One of the challenges of treating cancer is how to destroy malignant tumors without harming healthy cells. A new method that shows great promise for achieving this goal employs the use of a suicide gene. A suicide gene is a gene that causes a cell to be killed through apoptosis or programmed cell death (PCD). PCD is a series of biochemical events that cause cell membrane dissolution, cell shrinkage, and nucleus and DNA fragmentation. The process also involves cleansing the body of cellular debris.
Currently, two methods of suicide gene therapy are used. Enzyme-gene prodrug therapy (GDEPT) uses a gene taken from the cancer cell and then modified with other genes to form enzymes that are harmless to healthy cells. This foreign enzyme is inserted into cancer cells where it releases a prodrug, which is a small molecule that is harmless to healthy cells but destructive to cancer cells. The modified suicide gene converts the nontoxic prodrug into a cytotoxic substance.
The second method of suicidal gene therapy is called virus-directed enzyme-prodrug therapy. This uses a virus, such as herpes simplex or cold virus, as a carrier, or vector, to deliver the changed genes to the cancer cells. A study conducted by the Methodist Neurological Institute in Texas will use the herpes virus to deliver suicide genes to brain tumors. Patients will be given Valtrex, a drug used to treat the herpes virus. Suicide genes are expected to destroy cancer cells to such an extent that when the drug treats the herpes carrier, the cell should be destroyed.
Suicide gene therapy is not necessarily expected to completely eliminate the need for chemotherapy and radiation therapy for all cancerous tumors. The damage inflicted on cancer cells, however, makes them more susceptible to chemo or radiation. This approach has already proven effective against prostate and bladder cancers. The application of suicide gene therapy is being extended to several other forms of cancer as well.
Cancer patients often have depressed immune systems, so they can experience some side effects of using a virus as a delivery agent. Experiments have been conducted using a polymer as an alternative support. A polymer is a biomaterial that mimics a virus, but is safer as a delivery agent. This has also proven effective with bladder and prostate cancers.
The existence of a different type of suicide gene is also being explored as a possible explanation for the higher incidences of suicide in some families. Although most psychiatrists believe that suicide can have several causal factors, there is a trend for higher instance of suicide among related parties and in some geographic regions. For example, the suicide rate in Hungary and Finland is higher than in any other reporting country.
A 20-year Canadian study of patients being treated for depression found that patients with a serotonin-2 (5-HT2A) gene mutation were twice as likely to attempt suicide as patients without this genetic difference. Patients with the serotonin mutation had an overabundance of receptors, resulting in improper uptake of serotonin. Studies also showed that patients with variants in two genes, GRIK2 and GRIA3, were more likely than other patients to attempt suicide while taking certain antidepressants.
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