Thursday, June 5, 2014

Cancer and Personalized Medicine

If you recall we spent week five of the course discussing the different treatments available for those who have cancer. During the week, we discussed the three most common methods of treatment, those being: surgical oncology, radiation therapy, and medical oncology. Surgical oncology mainly takes place as a treatment in the form of a resection of a solid tumor with wide margins to ensure complete removal. Radiation oncology uses x-rays and carbon ions to directly damage DNA of the cancer cells in hopes the damage will prevent continued growth. Lastly, we discussed medical oncology, wherein we discussed chemotherapy. When we discuss personalized medicine we are generally referring to changing the way in which we use medical oncology.
Today if you are in the unfortunate circumstance that you have cancer, the way in which you are treated for that cancer doesn’t have a lot to do with who you are. It will vary depending on what type of cancer you have, yes, but nothing to do with you as a person. The doctor will give you the same treatment to those who have the same cancer, at the same stage as you.  This is due to the precedents within the “standard of care” which involves finding and administering the best treatment for the general population. For example, pre-emptive measures for breast cancer include self-exams until age 40 when mammograms become the standard and, if diagnosed, surgical oncology and medical oncology (chemotherapy) are recommended. In many cases this standard of care may be the safest, most sensible option. However, while you may have the same type of cancer as the other patient in the waiting room, you are not the same person as them, and this is what personalized medicine tries to focus on by incorporating a person’s genetic makeup.
At its core, personalized medicine is an approach that emphasizes the ways in which your disease risks are unique and different, based on the predispositions written into your genome at birth. Its emphasis is then transcribed into an action of prevention, diagnosis, and treatment that is very specifically designed for you. Because of the human genome project we have identified every genome in the human sequence. This and other advancements have made it so anyone can have their personal genomes scanned and fully sequenced. These genetic tests could lead to successful medical oncologic treatments (like drugs) rather than surgery. For example, liver can be BRAF positive and if this is identified then you could take sorafenib, an FDA approved drug by disabling the BRAF kinase domain. It does this by preventing ATP from binding and, hence, locking the enzyme in its active form. In a different case, cystic fibrosis patients have a mutation in the CFTR gene. This causes the over secretion of mucus, impeding the lungs and pancreas, leading to labored breathing and the pancreas’s inability to absorb what it needs from food. Thanks to studies done on the CFTR gene, researchers have found a mutation that’s found in 4% of cystic fibrosis patients. The mutation is caused by the amino acid glycine (at 551) being replaced with an aspartic acid. Specifically for G551D, the protein is brought to the epithelial cell surface (the correct destination), but protein cannot transport chloride through the ion channel. Ivacaftor promotes the transport of chloride through the ion channel by binding to the channel, which increases the chance that the ion channel remains open.
In the method of prevention, I think that the prime example stems from breast cancer. Those who are carriers of a BRCA1 mutation are at a 65% risk of breast cancer and 39% of ovarian cancer. Generally, it is not until after they find an anomaly in mammogram that they test for the BRCA1 mutation. However, with the ease of testing now, if testing for the BRCA1 mutation became apart of one’s first physical it could warrant starting mammograms before the age of 40 and making them more frequent than once a year. This would help to catch the breast lump as a carcinoma in situ, providing a much better outcome for the patient in that he or she might not need chemotherapy.

In the case of cancer, great strides have come from the incorporation of genetics into medicine. We have seen a couple cases in which genetic testing could be, and has been, used helped to improve the outcomes of those who have taken the advantages of personalized medicine. One of its pitfalls is that in a recent study by GfK (a global research firm), only 4% of those questioned knew what Personalized medicine was based on the definition “medicine based on genomic makeup”. In addition, those that do know about its possible positives want to see evidence before you’re willing to move away from the tried and true methods of treating cancer.


McMullan, Dawn. "What Is Personalized Medicine?" Genome Spring 2014 (2014): 34-39. Web. 1 June 2014.

Morton, Carol C. "Dana-Farber/Harvard Cancer Center: The Future of BRAF Inhibitors." The Future of BRAF Inhibitors. Harvard University, n.d. Web. 1 June 2014.

Verma, Mukesh. "Personalized Medicine and Cancer." Journal of Personalized Medicine 2.1 (2012): 1-14. Web.