What is a Suicide Gene?

One of the challenges of cancer treatment is how to destroy malignant tumors without damaging healthy cells. A new method that shows great promise for accomplishing this employs the use of a suicide gene. A suicide gene is a gene which will cause a cell to kill itself through apoptosis, or programmed cell death (PCD). PCD is a series of biochemical events which cause the cell membrane to dissolve, the cell to shrink, and the nucleus and DNA to fragment. The process also provides for the body’s cleanup of the cellular debris.

There are currently two methods of suicide gene therapy being used. Gene-directed enzyme-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 the tumor cells where it releases a prodrug, which is a small molecule harmless to healthy cells, but destructive to cancerous cells. The modified suicide gene converts the non-toxic prodrug into a cytotoxic substance.

The second method of suicide gene therapy is called virus-directed enzyme-prodrug therapy. This uses a virus, such a herpes simplex or cold virus, as the carrier, or vector, to deliver the modified genes to the cancer cells. A study being conducted by Methodist Neurological Institute in Texas will be using herpes virus to deliver the suicide genes to brain tumors. The patients will be given Valtrex, a drug used to treat the herpes virus. The suicide genes are expected to break down the tumor cells to such a degree, than 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 treatment for all cancerous tumors. The damage inflicted upon the tumor cells, however, makes them more susceptible to the chemo or radiation. This approach has already proven effective against prostate and bladder cancers. The application of suicide gene therapy is being expanded to several other forms of cancer as well.

Cancer patients often experience depressed immune systems, so they can suffer some side effects of the use of a virus as a delivery agent. Experiments have been conducted using a polymer as an alternate carrier. 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 kind of suicide gene is also being explored as a possible explanation for the higher instances of suicide in some families. While most psychiatrists believe that suicide may have several causal factors, there is a tendency for a higher instance of suicide among related parties and in some geographic regions. For example, the rate of suicide in Hungary and Finland is higher than in any other reporting country.

A 20-year Canadian study of patients being treated for depression did discover that patients with a mutation of the serotonin-2 gene (5-HT2A) were twice as likely to attempt suicide as patients without this genetic difference. The patients with the serotonin mutation had an overabundance of receptors, resulting in an improper absorption of serotonin. Studies have also shown that patients with variants in two genes, GRIK2 and GRIA3, were more likely than other patients to attempt suicide while taken certain antidepressants.