Suicide gene

Activation of a suicide gene can cause death through a variety of pathways, but one important cellular "switch" to induce apoptosis is the p53 protein.

Suicide genes form the basis of a strategy for making cancer cells more vulnerable or sensitive to chemotherapy.

[1] Most suicide genes mediate this sensitivity by coding for viral or bacterial enzymes that convert an inactive drug into toxic antimetabolites that inhibit the synthesis of nucleic acid.

Necrosis occurs when a cell is damaged by an external force, such as poison, a bodily injury, an infection or getting cut off from blood supply.

They break down the cellular components needed for survival, and they spur production of enzymes known as DNase, which destroy the DNA in the nucleus of the cell.

When cells recognize viruses and gene mutations, they may induce death to prevent the damage from spreading.

One of the most promising therapeutic strategies in this regard is cancer suicide gene therapy (CSGT), which is rapidly progressing into new frontiers.

Main mechanisms inducing cancer cells' deaths include: transgenic expression of thymidine kinases, cytosine deaminases, intracellular antibodies, telomeraseses, caspases, DNases.

For example, a commonly studied strategy based on transfection of herpes simplex virus thymidine kinase (HSV-TK) along with administration of ganciclovir (GSV), in which HSK-TK assists in converting GCV to a toxic compound that inhibits DNA synthesis and causes cell death.

For instance, the most researched immunotoxin for cancer therapy is the diphtheria toxin as it inhibits protein synthesis by inactivating elongation factor 2 (EF-2) which in turn inhibits protein translation,[6][9] Moreover, p53 is identified to be frequently abnormal in human tumors and studies show that restoring function of p53 can cause apoptosis of cancer cells.

[6] Suicide gene therapy is not necessarily expected to eliminate the need for chemotherapy and radiation treatment for all cancerous tumors.

Cancer patients often experience depressed immune systems, so they can suffer some side effects of the use of a virus as a delivery agent.

In the last few years, cell-mediated gene therapy for cancer using mesenchymal stem cells (MSCs) was patented.

[8][12][13] As hundred percent transduction of all tumor cells is very difficult to achieve, BE is critical feature of suicide gene therapy.

The drug is supposed to show high specificity towards cancer in order to effective, but studies have shown this to be rarely achieved.

Additionally, poor accessibility to target cells is an important limitation of suicide gene therapy.

Another major hurdle of suicide gene therapy is partial vector specificity to target affected cells.