Genetics: Epigenetic Drugs and their Fight Against Breast Cancer
Epigenetic changes, such as histone methylation and acetylation, alter gene expression which can silence genes completely. Disturbance of epigenetic events can result in cardiovascular disease, neurological disorders, metabolic disorders and, of course, cancer development (Genet Epigenet. 2014, June). Identifying drugs that inhibit the epigenetic changes that cause these fatal health issues are of great interest in the clinical and pharmaceutical world. Six epigenetic drugs have been found and are currently in use to fight these diseases, but in this report we shall be concentrating on the use of epigenetic drugs on breast cancer development. We shall discuss the science of the use of two inhibitors that reverse the epigenetic changes in the body, ultimately treating the disease.
Background
Epigenetics, literally meaning “on top of genetics”, are in simple terms the element of DNA (deoxyribonucleic acid) that gives the instructions to the genes of what they have to do. At this moment there are five different drugs in use against diseases such as cancer which have been caused by epigenetic mutations; DNA methylation inhibiting drugs, bromodomain inhibitors, histone acetyl transferase inhibitors, histone deacetylase inhibitors, protein methyltransferase inhibitors and histone methylation inhibitors. But for the purposes of this report, we shall only be focusing on histone deacetylase inhibitors.
DNA methylation is a process that causes most cancers, in which a CH3 molecule attaches itself to a strand of DNA and ables itself to turn off certain epigenetic instructions. In breast cancer, the mutation specifically targets the gene P53, causing a loss of cell’s ability to repair DNA. This then leads to the development of cancerous tumors located in the breasts.
As far as cures using epigenetic drugs are concerned, when histone deacetylase is used in combination with calpeptin, two chemically distinct histone deacetylase inhibitors, cell death increases by inducing cell-cycle arrest and apoptosis (Anticancer Res. 2012 July) (HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics.). Collectively, these results showed that the combination of HDACi and calpeptin inhibited the growth of two distinctly different types of breast cancer cells and could have wide clinical applications, though the mechanisms of inhibition are possibly different.
Ethical/Social(?) Pros and Cons
Although epigenetic drugs are some of the most scientifically important and cutting-edge subjects of scientific discovery, they don’t come without their legal, ethical and social implications.
Epigenetic mechanisms are important for normal development, and thus the disruption of epigenetic processes can lead to detrimental consequences. By using epigenetic drugs and inhibitors to cure tumors in the breasts, situated close to the heart, it may in turn disrupt another epigenetic mechanism and lead to further health problems in the subject such as cardiovascular disease. Their cancer may be cured, but they may development cardiovascular diseases in the near future after treatment. This raises the argument of whether epigenetic treatment is worth it if the patient already has minor cardiovascular problems, or even not.
The debate has also been up in the epigenetic community as to whether those whose breast cancer has not developed to the level where chemotherapy is neither effective nor viable. And to add to that, should epigenetic drugs be used even before the growth of a tumor has begun or should it’s cancer fighting potential be saved until after the patient has been diagnosed? This ethical and social issue is still a raging debate in the scientific community, but personally I believe the drug should be reserved for patients whose chemo treatment has failed, purely because of the minor risk of heart complications developing.
Conclusion
Epigenetic drugs and their uses are an exciting new avenue of scientific exploration that has already demonstrated huge medical innovations in breast cancer. In my opinion, the risks don’t outweigh the benefits of using epigenetics to boost the development of the cure of breast cancer, although in terms of whether a non infected person should be subjected to epigenetic treatment as a prevention method I regard the risk as too great for further health complications for it to be worth it. A continuation of the study of histone deacetylase inhibitors and other epigenetic drugs could prove to create a future without breast cancer.
Information References
Heerboth, S., Lapinska, K., Snyder, N., Leary, M., Rollinson, S., & Sarkar, S. (2014, May). Use of Epigenetic Drugs in Disease: An Overview. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251063/
Mataga, M., Rosenthal, S., Heerboth, S., Devalapalli, A., Kokolus, S., Evans, L., . . . Sarkar, S. (2012, July). Anti-breast cancer effects of histone deacetylase inhibitors and calpain inhibitor. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22753709/
Rothstein, M. A., Cai, Y., & Marchant, G. E. (2011, February). THE GHOST IN OUR GENES: LEGAL AND ETHICAL IMPLICATIONS OF EPIGENETICS. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034450/
Image References
Fig. 1 - DNA methylation [Image]. (2009, January 7). Retrieved from
http://www.ks.uiuc.edu/Research/methylation/
Fig. 2 - [P53 Gene Mutation]. (2007, January 25). Retrieved from
http://scienceblogs.com/grrlscientist/2007/01/25/post-7/
Fig. 3 - HDAC [Image]. (2016). Retrieved from
http://www.pharmstatus.com/HDAC.php