Gene Therapy for Cancer

What is Gene therapy?

The source of many human illnesses is found in our genetic structure. What has been previously considered inaccessible for the human: the genetic material from which we are all made of – is now at the forefront of medicine.

Gene therapy refers to ways of utilizing genes to treat illnesses by changing human hereditary material. Gene therapy is the insertion of normal or genetically altered genes into cells to replace the defective genes which causing cancer spread and tumor growth.

Cancer = Malfunction of our Genes (DNA)
Cancer is a term for a group of diseases in which abnormal cells divide without control and invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems.

Cancer begins in our cells, the body’s basic unit of life. Normally, cells grow and divide as part of the normal process of cell regeneration which keep our body healthy. When cells become old or damaged, they die and are replaced with new cells.

However, sometimes this normal process goes wrong. The genetic material (DNA) of a cell can become damaged or changed, producing mutations that affect normal cell growth and division. When the DNA of a cell is damaged, cells do not die when they should, and more cells are forming when the body does not need them. These extra cells may develop into a mass of tissue called a tumor.

While some tumors are benign and can be removed from the body without further spreading, other tumors, called malignant tumors, are cancerous; they can invade healthy tissues and spread to other parts of the body (Metastasis).

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth.

P53 Gene - the “Genome guardian.”
The last two decades of research in genetics and molecular biology have given us an unprecedented knowledge on the inner workings of cells and the role of the genetic information that is encoded in them. Genes, the biological units which hold that information, hold a key role in the understanding of how diseases are formed, as well as the key to new medical solutions.
Tumor Suppressor Genes are special genes which are in charge on slowing down cell division, the repair of DNA mistakes and the elimination of old or damaged cells. When tumor suppressor genes don’t function properly, an uncontrollable cell growth may occur, which may lead to cancer. Among about 30 tumor suppressor genes that have been identified, the most potent member of these group and the most studied one is a gene called p53 gene. p53 gene act to kill cancer cells, suppress cancer cell growth and prevent cells from becoming cancerous. After more than two decades of study, the p53 gene is widely regarded as the “genome guardian.”
It has been estimated that at least half of all human malignancies are related to a mutation of the p53 gene. It is the core principle of Gene therapy for cancer to repair the malfunctioning of this natural genetic guardian.

“Gendicine”
“Gendicine” is a drug composed mainly of human normal p53 tumor suppressor gene and modified adenovirus serotype 5, which acts as a vector delivering the therapeutic p53 gene into target cells.
The p53 gene is involved in multiple cellular processes, including control of cell division, DNA repair, cell differentiation, genome integrity, apoptosis, and inhibition of blood vessel growth, or anti-angiogenesis. It brings forth its anti-tumor activities by one or more of the following ways:

1. Causing cancerous cells to self-destruct:
The p53 gene triggers apoptotic (programmed cell death) pathways in tumor cells by a *transcription-dependent mechanism in the cell nucleus, in the cell mitochondria and in the Golgi apparatus (a system involved in intercellular transport).

2. Triggering the activity of the Natural Killer Cells (NK) to fight the cancerous cells:
The p53 gene can trigger immune-response factors that will alert the natural killer cells to identify the cancerous cells and act to destroy them.

3. Preventing and inhibiting normal processes of DNA repairs and anti-apoptosis functions inside cancerous cells, which interfere with the development of tumors.

4. Preventing and inhibiting the tumor’s defense and propagation mechanisms:
The p53 gene has the ability to:
(1) Decrease the tumor’s resistance to radiation and chemotherapy drugs.
(2) Blocking blood supply to tumor’s tissue.
(3) Suppressing tumor cell adhesion, infiltration and metastasis.

5. Blocking the communication signals in tumor cells: by interfering inter-cellular communication within cancerous cells the p53 gene cut off cell cycle and prevent its growth.

6. Hindering the tumor cells nutrition uptake:
The p53 gene has the ability to limit glucose uptake, and the production of ATP in tumor cells.

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