However none of these can guarantee a 100 removal of cancer cells within the breast or surrounding tissue and a patient suffers from significant side effects after treatment.
Through the use of viral vectors, Gene Therapy is being looked at as an alternative treatment for breast cancer with the potential, unlike the other treatments, to get rid of all the cancerous cells within an individual.
If a vector is found with all the correct characteristics, not only can this be a breakthrough for breast cancer, but for most types of human cancer.
Introduction
Identifying the underlying cause(s) of human cancer has been puzzling mankind for centuries. However, over the past 10 years great strides have been taken in that field. One form of human cancer is the cancer of the breast. Breast cancer is now the most common cancer in the UK, with around 48,000 new cases diagnosed each year and around 12,000 deaths a year as a result of it. Treatment options for this disease are surgery, chemotherapy, radiotherapy and hormone therapy. These treatments all come at a cost with their side effects and none are guaranteed to completely eradicate all the tumour cells within the breast and surrounding tissue. Therefore is it then possible to come up with a treatment that can fully treat breast cancer and at the same time have no major side effects? This report focuses on the possibility of using gene therapy as a legitimate cure for breast cancer and the possibility of being a universal treatment for human cancer.
Methodology
A variety of methods were used when collecting information for this paper. Up to date research papers and journals were used and accessed via PubMed, the University search engine MetaLib and Google Scholar. Science direct was also used. The search terms I used were "gene therapy", "breast cancer", "BRCA1", "BRCA2" and "p53".
Gene therapy
To put it simply, gene therapy involves replacing a defective gene with a normal working gene in order to treat a disease. Of course it isn't as simple as that as there are many ways in which this process can be carried out and deciding which one is the best or which one carries the least risk is still an on-going debate.
Currently gene therapy is used to treat major diseases such as cystic fibrosis but this report will focus on the potential of it being used as a treatment for human cancer, specifically breast cancer.
At this moment in time the current treatment options for breast cancer are surgery, radiotherapy, chemotherapy and hormone therapy. Once screening has confirmed a cancerous lump within the breast, Surgery is usually the first line of defence. The surgery, either lumpectomy or mastectomy, is known to be very painful and, depending on the size of the cancerous mass within the breast, reconstruction of the breast may be required afterwards. The 3 other treatments are known as adjuvant treatments and are given usually after surgery. Radiotherapy and chemotherapy kill of any cancerous cells in the breast that were not removed during surgery using radiation and drugs, known as cytotoxins, respectively. While this has been proven to reduce the risk of recurrence of breast cancer further on in life, certain side effects like losing your hair after some forms of chemotherapy have effects on patients a long time after the treatment is complete. Hormone therapy is used to either reduce the activity of oestrogen and progesterone (which are known to stimulate rapid cell growth) or reduce the activity of cells which bind to them. This has also proven to be affective but patients produce signs of menopause during treatment.
Despite advancements in medicines, screening and surgical techniques, none of the above treatments can guarantee a complete eradication of cancerous cells within an individual's body. This is maybe due to the focus being on treatment rather than prevention. Is it then feasible to think that there is a breast cancer treatment out there that can not only cure the cancer fully, but can also result in no significant side effects for the recipient?
Vectors
Gene therapy involves replacing a faulty gene with a normally functioning gene through the use of vectors. Vectors are best described as vehicles which transfer the healthly gene to the body. There are many types of vectors and they fall into two categories: viral and non-viral. Viral vectors are more commonly used in cancer gene therapy due to the fact that they have higher transfection efficiency. This means they are able to transduce more cancer cells than the non-viral proteins. In this report I will be focusing on the 2 most commonly used viral vectors - retroviral and adenoviral.
Retroviruses are the most commonly used of the viral vectors and have the ability to integrate into the host genome in a stable fashion. They contain reverse transcriptase which allows the integration into the host genome. Disadvantages of using retroviruses as vectors include their relatively poor efficiency can be overcome by the development of pseudotype retroviruses.
Adenovirus DNA does not integrate into the genome and is not replicated during cell division. They are the secondly most common viral viruses. Despite good characteristics such as having very high transfection efficiency, they cause immunological and inflammatory reactions which make it impossible to repeat administrations in clinical trials.
The three genes I am going to concentrate in this report are BRCA1, BRCA2 and P53.
BRCA1 and BRCA2
These two are human genes that belong to a class of genes that are known as tumour suppressors (prevent formation of tumours). Most inherited cases of breast cancer are connected with a malfunction in these two genes. In a healthy individual, one of BRCA1's functions is to keep breast cells growing normally and one of BRCA2's functions is to repair chromosomal damage within a cell. The problem arises when these genes undergo a harmful mutation or abnormality. The genes don't function normally and when they are passed on from generation to generation, the risk of breast cancer increases due to the fact that the risk of uncontrollable cell growth and growth of a tumour also increases.
Ideas that gene therapy could be a possible treatment method for breast cancer stemmed from studies that showed that over expression of BRCA1 and BRCA2 into the sporadic breast results in growth inhibition and tumour suppression. As of yet, the mechanism of the growth inhibition is unknown.
Injection of BRCA1 retroviral vector in mice that suffered from breast and ovarian cancer produced tumour inhibition. This led to initial human phase 1 clinical trials being carried out. These trials of the BRCA1 retroviral gene showed us that there is a potential for gene therapy and that retroviral gene therapy is safe. However, it also showed us that a lot more trials and research is needed before this type of therapy can be successfully implemented on human sufferers. The issue of the retroviruses causing an immune response from healthy patients also came up and this is an obvious problem - short term because it affects the vectors stability and long term as repeat administration will not be possible.
P53
P53 is a gene that is mapped on chromosome 17 and, like BRCA1 and BRCA2, it is also a gene suppressor. This gene is different to the other two in the sense that it is found in 70% of tumours where as BRCA1 and BRCA2 are specific to certain cancers. When p53 is normal, it binds to the cells DNA and that stimulates another gene to produce a protein called p21. P21 interacts with a cell-division stimulating protein called cdk2 and this interaction makes the next stage of the cell division not possible and therefore uncontrollable cell division is prevented.
When p53 is harmfully mutated, it can no longer bind to the cell's DNA and that leads to the other reactions in the cycle not occurring and there will be no stop signal for cell division. The result of this will be uncontrollable cell division which will lead into a tumour formation.
Mice with tumours in their breasts and cell cultures have been used to administrate a recombinant adenovirus containing the human gene p53. The results indicated that the mechanism was safe and efficient to use. 5 years of clinical trials resulted in the formation of gendicine. Gendicine is a drug that is made up of the adenoviral vector and the human p53 suppressor gene. The p53 suppressor gene is carried by the adenoviral vector into the tumour cells. Once inside the tumour cells, p53 is has many functions that stop the cancer from spreading. It causes self destruction of the cancerous cells by triggering apoptosis in the tumour cells. It also prevents the tumour cells from developing and hinders the cancerous cell's function by inhibiting DNA repair and limits the uptake of glucose and ATP production respectively.
Conclusion
The vibes that I am getting having read several up to date journals and articles is that the bid breakthrough is just around the corner. If a vector that is found with all the right characteristics and no/minimal disadvantages then using gene therapy as a cure for the majority of human cancers will become a real possibility. Unlike the other current treatments, gene therapy has the potential to get target and destroy all the cancer cells in an individual's body. Another appealing aspect of gene therapy, if it is administered intravenously, is that it continues to search for cancer cells and destroy them over a period of time. Currently, it is a matter of time before gene therapy is used in conjunction with another treatment
