Chemotherapy is currently the most common cancer treatment. This involves the administration of various anti-cancerous chemicals which are highly toxic. Although single drugs can be utilized, a cocktail of numerous chemicals is often more effective. However, this increases the toxicity, and many adverse effects occur on the patient. Chemotherapy involves the use of chemicals which are known cancer-fighters, or chemicals which enable the cells and tissues around a certain cancer to better fight the cancer. In other words, it makes the cancerous area a more favourable battle ground for the patient. An example of a chemotherapy agent is Vinblastine, a chemical which targets leukemia, lymphoma, breast, and lung cancers. (14) The side effects of various chemotherapy agents, such as Vinblastine, include nausea, anaemia, lowered resistance to infection, fatigue and a general feeling of being week. (14) Some chemotherapy agents also inhibit the division of cells in the body, thus demonstrating the characteristic hair loss and low immune system. Chemotherapy is a commonly used cancer treatment; gene therapy could be the cancer treatment of the future.

Gene therapy is the process of inserting genetic material into an organism in order to alter genetic code. (1) The modification of the genome (a change in its structure) will change how it codes everything in the organism (function). An example of this expression of the structure-function relationship is the correction of genetic defects that result in the malformation of proteins. The most common method is to insert a gene into the nonspecific portion of the genome: in other words, the non-functional portion of our genes becomes helpful. (1) This can be done by splitting a genetic helix (figure 1) and exchanging genetic portions or inserting a gene within the helix. The portions (detailed in Figure 2) exchanged are the interior of the helix, which then recombines. The atomic genetic helix (Figure 3) outlines how the chemical composition can be easily altered (theoretically) in order to accommodate changes in the genetic coding.

Figure 1: Genetic helix. Figure 2: Detailed genetic helix. Figure 3: Atomic genetic helix.

Viral Gene Therapy

Gene therapy is frequently conducted with viruses, but has been known to be performed using bacterial vectors as well. (7) Different viruses affecting humans target different parts of the body, such as respiratory or intestinal, due to molecular flags that the viral receptors look for. If the location of a cancer is known, then the specific types of viruses could be utilized to target that area in order to correct the genetic error. The genetic material within a virus can be exchanged for different genetic material: thus accomplishing a different purpose.

For example, an intestinal cancer could use the viral shell of a virus that specifically targets intestine cells; instead of injecting an illness, however, the modified DNA within the virus would be injected into it and correct the genetic disorder causing cancer.
The specific locations for certain cancers can be located by methylating the sample DNA.

(5) Due to the lengthy explanation of the methylation of DNA,
I will not go into further detail, other than it is simply chemical methylation:
the introduction of CH3.

For example, if the gene EPHA3 (a combination of different molecules specifically structuring genetic material using nucleic acids) at the map 3p11.2 were to be methylated (using chemical methylation), leukemia would be a result.

Using this knowledge, gene therapy could be implemented in order to counter-act the leukemia at map 3p11.2. (4, 5) The genetic map is simply the location of a gene within the genome relative to the other genes.

There are many different types of viral vectors used in viral gene therapy:

• Retroviruses - A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells. Human immunodeficiency virus (HIV) is a retrovirus.
• Adenoviruses - A class of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans. The virus that causes the common cold is an adenovirus.
• Adeno-associated viruses - A class of small, single stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19.
• Herpes simplex viruses - A class of double-stranded DNA viruses that infect a particular cell type, neurons. Herpes simplex virus type 1 is a common human pathogen that causes cold sores. (1)

These viral vectors find their host cell through the use of the receptors on the target cells in the designated cellular surface. The virus then slips through the semi-permeable membrane of the cell and injects the DNA into the nucleus of the cell.

(10) Figure 4: Gene therapy using an adenovirus vector.

Figure 4 outlines the use of an adenovirus vector in viral gene therapy. This emphasizes the huge change in the virus’ original function when contrasted with figure 5. The genetically modified virus no longer tries to take over the cell and replicate; it simply injects the DNA required without the destruction of the cell. This is because the gene in the original virus is what mechanised the creation of more viruses and, ultimately, the destruction of the host cell. Since this DNA was exchanged, it now functions as it was engineered to.

Figure 5: General virus functions.

Alternative Gene Therapy

There are many other methods of gene therapy. A brief outline of these includes the direct insertion of a gene by soaking a tissue in a solution containing high quantities of the desired DNA. However, due the economic purposes it is not feasible. It is expensive and the tissue has to be taken and then re-inserted into the patient, or the individual will be a walking genetic reaction if the tissue is drowned within his body (figure 6). As well, only certain (few) tissues accept this method for the acquisition of genes. (1)

Figure 6: The genetic modification of cells; the re-introduction of these cells into a patient.

Alternatively, there is also the use of bacteria, which is very similar to the use of viral vectors. They both have their genetic structure modified, and they both inject the gene into their target cell. Bacteria are more difficult to make target-specific, however, and thus are less favoured. (4)

Cancer

Cancer is one type tissue which has differentiated away from its original purpose. What is special about cancer is that it undergoes mitosis without self-termination. As such, this tissue becomes invasive on other surrounding tissues, often destroying it to make room for itself. Figure 7 an example of the invasive nature of cancer. (12)

Figure 7: Various stages of cancer.

A cancerous cell is determined by its inability to self-terminate. As this cell divides, it creates another cancerous cell, until there is a tissue of cancerous cells. This tissue develops its own vessels in order to take blood from its surroundings and feed itself for its further growth. The root of the problem, however, is that the “suicide gene” is deactivated. The suicide gene cannot be targeted itself, but the cancer itself can be targeted. There are many targetable proteins on cancer, in which the proper modifications to a virus could become attractive. (3)

Cancers can be targeted by the specificity of the cancer. Cancers have different methods of becoming cancerous, and below is a list of the number of known cancer genes to date distinguished by their method of mutation. For instance, the amplification section lists the 7 known cancer genes which are amplified. An example of such would be ovarian cancer. When an individual has ovarian cancer, a cancer gene is amplified and can thus be identified. (2)

Cancer Gene Census

Sorted By

• Amplification
• Chromosome
• Frameshift Mutation
• Germline Mutation
• Large Deletion
• Missense Mutation
• Nonsense Mutation
• Other Mutation
• Somatic Mutation
• Splicing Mutation
• Symbol
• Translocation

Number

• 7
• 367
• 67
• 68
• 28
• 87
• 63
• 10
• 330
• 42
• 367
• 275

Cancer is developed through a stepwise mutation of one cell. It is only when this cell divides that the cancer starts to become a cancerous tissue. Many times our body gets rid of the malignant cell before it develops into a cancerous tissue, but when the cell divides without getting destroyed, cancer results. (11) See figure 8 for an outline of cancerous mutation.

Figure 8: Progressive cancer mutation.

Figure 9: Cancerous neuron.

Figure 9: a brain cancer cell. Figure 10: a cancer cell being attacked by the immune system.

Figure 10: Breast cancer cell attacked by immune system.

Current Research

Today there is already some research into fighting cancer with gene therapy. This included methods which embed DNA which enable surrounding tissue to attack cancer cells, as well as targeting the cancer itself and attempting to weaken it enough for your body to better fight it off. (8)

One of the most interesting approaches to curing cancer with viral gene therapy is the introduction of a “suicide gene” into the cancer, thus causing it to self terminate; this allows for the body to heal over the damaged spot while the cancer continues to remove itself. (8)

Viral gene therapy is not limited to curing cancer, however. This method is being used to cure other genetic diseases. In fact, the very first clinical trial for viral gene therapy was on the disease ADA, a serious and rare genetically imposed immunodeficiency disorder. (8)

Due to the potential dangers of viral gene therapy (such as the accidental introduction of a gene into a different cell or tissue), laborious steps have to be taken before a clinical trial is considered, and extensive trials are made following approval. So far, there have been no uses of viral gene therapy outside of clinical trials. (8)

Conclusion

Due to the genetic mutation which causes cancer, viral gene therapy appeals to be an appealing method to attempt to cure it despite the risks during the clinical trials. Gene therapy also seems a promising route to cure or help cure any genetic disorder. However, the risks are high, as the insertion of an unstable gene could result in a mutation which could worsen the conditions instead of treat them. As such, gene therapy is a very promising and real opportunity; with great promise comes great risk, however. Hopefully the use of viral gene therapy can help make cancer a pandemic for the history books.