Special genes, called oncogenes, stimulate the production of growth-stimulating chemicals that trigger cell division. If an oncogene is irreversibly switched on, it can cause uncontrolled cell division and lead to the formation of a cancer. It is generally thought to be an irreversible process, that's why the cure is to kill or excise these cells (tumors) before they spread throughout the body (metastasize).
Lot's of research is focussed on trying to identify cancer cells before they mutate and are able to start multiplying, but there are also many new techniques being explored in gene therapy:
"Gene therapy is treating cancer by:
- Blocking abnormal genes in cancer cells.
- Repairing or replacing abnormal genes in cancer cells.
- Encouraging even more genes to become abnormal in cancer cells so that they die or become sensitive to treatment.
- Using viruses to carry treatment-activating enzymes into the cancer cells. The cancer cells would then either return to behaving normally, or die off because of other damage in the cell.
The genes that are damaged may be:
- Genes that encourage the cell to multiply or 'oncogenes'
- Genes that stop the cell multiplying or 'tumour suppressor genes'
- Genes that repair other damaged genes
Gene therapy and oncogenes:
Instead of trying to repair damaged oncogenes, scientists are trying to find drugs that can block the proteins that the oncogenes keep on making. They think this may be easier than trying true gene therapy and replacing the damaged oncogenes. But the body's cells make hundreds of different proteins that are all very similar. The difficulty is in finding a drug that will not block normal proteins and so have toxic side effects. Laboratory work is going on and these treatments may start to become available in the next few years.
Gene therapy and TS genes:
The tumour suppressor gene p53 is damaged in most human cancers. A lot of work has been going on into how to replace the damaged p53 gene with a normal one. But the scientists have to find a way to do this. Viruses have been used in the laboratory to carry the new gene into the cancer cells. If used in people, these carrier viruses are weakened so they cannot multiply and cause disease. But weakened viruses might be killed by the immune system before they had a chance to carry the new gene to the cancer cells. Some of the research work that has needed to be done has been to try to find a balance between.
Stopping the carrier virus causing disease:
Making sure the carrier virus is strong enough to get past the immune system without being killed. Early clinical trials are now in progress looking at treating cancers with modified p53-producing viruses. These trials are still investigating the technical side of developing the treatment - using the carrier virus to get the genes into cells for example. These are early days and this is a long process, unfortunately.
Gene therapy and 'repair' genes:
Gene therapy could be used to replace the damaged DNA repairing genes. But another approach, once these genes have been identified, is to damage even more of them. Even a cancer cell dies if it has too many mutations to its DNA. And if its repair genes are all damaged then it will carry on mutating until it dies. Or becomes more easily killed by other cancer treatments such as radiotherapy or chemotherapy. Laboratory work in going on, but clinical trials are still a little way off.
VDEPT:
This type of treatment is becoming more common, although it is still only given within clinical trials. It stands for 'Virus Directed Enzyme Prodrug Therapy'. A modified (harmless) virus is used to carry an enzyme into the cancer cells. Once the enzyme has found its way to the cancer cells, an inactive form of a chemotherapy drug, called a 'prodrug', is given to the patient. When the inactive prodrug reaches the cancer cells, the enzyme converts the prodrug into the active chemotherapy drug, so that it can kill the cancer cell. The idea behind this type of treatment is that it is targeted only to cancer cells. These are the only cells in the body that have the enzyme capable of converting the prodrug. As normal body cells should not be affected, there should not be too many side effects with this treatment. How effective this treatment is and whether there are side effects is being tested in the clinical trials that are now in progress in the UK and abroad.
Tackling immortality:
Scientists now know how cancer cells stay immortal. They have found the enzyme the cells use. If they can block or destroy the enzyme, then the cancer cells will age and die off as normal cells do after they have doubled 60 or so times.
Tackling the cancer's blood supply:
Cancers encourage the growth of new blood vessels to bring them oxygen and food. This is called 'angiogenesis'. Drugs that stop angiogenesis called antiangiogenics are being developed.
Tackling cancer spread:
Cancer cells do not stick together as well as normal cells. The proteins that normal cells use to stick to one another are often missing in cancer cells. If these could be restored somehow, then the cancer may not be able to spread. If normal cells become unattached and float free, they tend to die off quite quickly. Scientists think an oncogene is responsible for telling the cells they are attached when they are not. If this gene could be repaired using gene therapy, or the protein it makes blocked by a drug, then free floating cancer cells would die. The cancer cells would not be able to spread away from the primary tumour.
Source: "Gene Therapy," Cancer Research UK, 04 March 2005.
http://www.cancerhelp.org.uk/help/default.asp?page=131
Also, new recent research has found a protein that may be able to prevent the replication of cancerous cells, but this is just a very preliminary finding and much more research and study needs to be done:
"An ancient protein could be critical to stopping the uncontrolled division of tumor cells that cause cancer. Molecular Biology and Microbiology professor Mark Muller has found that the protein, called MKRN1, promotes the destruction of an enzyme called telomerase that enables rapid duplication of cells. While researchers have known for years that healthy cells repress telomerase, they haven't understood why...."To the best of my knowledge, this is the first example of how the enzyme (telomerase) itself can be turned off," Johnson said.
The work focuses on the role that a long stretch of repeated DNA known as a telomere has in influencing cell length and, in turn, its lifespan. Each of the human's 46 chromosomes is capped on either end by telomeres, which help protect the cells. Each time a cell divides, the telomeres are shortened until eventually they become so small that the cell stops multiplying. Eventually the cell is eliminated from the body.
When telomere ends do not shorten, division continues unabated. The body contains other mechanisms that kick in to stop the errant reproduction unless the telomerase enzyme is present. In laboratory tests, the MKRN1 protein has eliminated the presence of telomerase in tumor cells, said Muller, who conducted genetic research at The Ohio Sate University for 25 years before joining UCF last summer. Muller said that the MKRN1 gene is incredibly ancient and has likely been part of a human genetic makeup since the beginning of time. "Many different species have these genes, which emphasizes important collective roles in life" Muller said. "Moreover, mutating or altering the MKRN1 gene is lethal, thus, cells cannot live without these genes, further supporting a key role in growth control and cancer."
Source: "Protein MKRN1 could stop replication of cancer cells," Cancer/Oncology News, 20 Apr 2005.
http://www.medicalnewstoday.com/medicalnews.php?newsid=23103