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Modern medicine has saved millions of lives, but with a little improvement, it could save even more. Our current medical practices rely on medical professionals reacting to a diagnosis, treating patients after they may be or already are ill. We are increasingly recognizing the necessity of being proactive in health care and this requires understanding how our bodies function, from the starting point – our genetics. Personalized medicine, also known as precision medicine or genomic medicine, is becoming an important step in this proactive medical approach. Personalized medicine is the idea of using a person’s unique DNA to determine which treatments and therapies would work best while reducing adverse drug reactions.
First, let’s take a step back to understand how our genetics plays into personalized medicine. Inside all of our cells is our DNA, a set of instructions on how to build us and keep us working. DNA is broken up into sections called gene. Genes are specific instructions on how to build parts of our body. If our DNA was a set of instructions to build a Lego city, the genes are the instructions to create each different Lego pieces needed to build the city. However, there can be different versions of genes. Version 1 of a gene may create a green lego brick, and version 2 may create a blue lego brick. Both bricks have the same structure and design, just different colors. Similarly, people have genes that determine eye color, but one version may give someone blue eyes, and another person green eyes. Different versions of genes is what makes people unique from one another. The study of genes and different versions of genes, is called genetics.
Many genes can create proteins, which are molecular machines involved in various activities such as repairing DNA, breaking down our food, and strengthening our immune system. Proteins can also function as entrances and exits for our cells. They interact with molecules like drugs and hormones on the inside and outside of the cell. These protein entrances and exits are a specific group of proteins called receptors, and behave like a lock, in that the correct molecule, or key, is needed to activate, or open, the receptor. Once the molecule fits in the receptor, a reaction occurs, either bringing the molecule into the cell, or causing a change inside the cell. In the figure below, we can see an example of the receptor (lock) and molecule (key), with the orange triangles only interact with the orange receptor, the purple with purple and pink with the pink. The blue circles are the cell wall.
Let’s now look at breast cancer as a real world example of protein receptors. Breast cancers can be divided into categories, depending on the protein receptors a patient’s cancer cells possess. In the case of the hormone estrogen receptor protein (ER), the two breast cancer categories are cancers with ER (ER+) and cancers without ER (ER-). Only certain drugs (keys) can bind to ER receptors (locks), and so only the patients who genetically possess these receptors (ER+), will respond to the drug treatment, while patients without these receptors will be unaffected, or potentially harmed as a result of adverse drug reaction. However, we wouldn’t know whether the patient has this ER receptor or not unless we test their genetics.
Cancers can be difficult to treat because if we don’t know their genetics, we don’t know which drugs will be effective against the cancers. An additional factor that makes treating cancers difficult is the varying genetics of the human population. Studies have shown that men and women respond to drugs differently, tend to present disease symptoms differently, and the same goes for people of different genetic backgrounds. However, most drug trials have been tested on caucasians and/or males. This means that drugs that are approved by the FDA for population cater to the physiology of either caucasians or males, but not necessarily everyone else in the population. This is why it’s important to have diversity in drug trials; different populations of people will have different DNA, and different DNA will result in different reactions (or no reactions at all) to medications and treatments. This study of the interaction of DNA and drugs is called Pharmacogenomics.
Dr. Minoli Perera of Northwestern University is one of many scientists who has recognized this deficiency in pharmacogenomics1,2. To close the inequality gap between patients, she started a coalition to increase African American genomics studies. This program is called ACCOuNT3 and stands for “The African American Cardiovascular Pharmacogenomics Consortium.” Its goal “is to ensure that all people, including African Americans, benefit fully from precision medicine.” Since focusing on genomic studies for African Americans and minority ethnic populations in the United States, Dr. Perera has identified an areas in the genome of African Americans that explains why they are at higher risk for certain cardiovascular diseases. One such disease is venous thromboembolism (VTE), a condition in which blood clots in veins, is the third most life-threatening cardiovascular disease in the United States, and affects African Americans 30%-60% more than other genetic populations in the United States. Dr. Perera has found genetic regions, or SNPs, in African Americans that lead to this increased risk4. Interestingly, these genetic regions are absent in those of european descent, further highlighting the importance of genetic diversity in any scientific study. While her research primarily focuses on cardiovascular diseases in African Americans, Dr. Perera’s approaches, program, and data can be further implemented to African American cancer patients.
Dr. Perera has also helped implement a trial program that is part of the patient database system, Epic. Called eMERGE, for Electronic Medical Records and Genomics (eMERGE) Network, this program includes genomic studies data and information of how effective drugs are based on a patient’s genetics. To determine which drugs a patient should receive for treatment, a physician will take a blood sample and run a basic genetic screen, and from this screen, the eMERGE program can identify which FDA approved drugs are more likely to help or hurt the patient. Not only is it important to know which drugs will help or hurt patients, but it is also important to know how much of a drug will affect the patient.
How might a future doctors visit look? Say you go for a routine check up. They may take a blood sample, and scan your genome for the types of genes you have. Based on your genetics, they can see which receptors you have and can look in a database to tell which drugs will treat you the best, with the least amount of side effects, and which drugs can and cannot be used together. It’s like a unique drug recipe for your body and your needs. However, with more research, personalized medicine can help with more than just which drugs work best for you. Precision medicine, as a preventative measure, can help you decide which diets are best for you, which exercises are best your your body and your metabolism. Everything about how your body works, comes from your unique genetics, and knowing them can help in developing not just medicine but lifestyle which is most suited for your unique needs.
- Gamazon, E. R., & Perera, M. (2012). Genome-wide approaches in pharmacogenomics: heritability estimation and pharmacoethnicity as primary challenges. Pharmacogenomics, 13(10), 1101-4.
- De, T., Park, C. S., & Perera, M. A. (2019). Cardiovascular Pharmacogenomics: Does It Matter If You’re Black or White? Annual Review of Pharmacology and Toxicology, 59(1), 577–603. https://doi.org/10.1146/annurev-pharmtox-010818-021154
- Friedman, P. N., Shaazuddin, M., Gong, L., Grossman, R. L., Harralson, A. F., Klein, T. E., … Perera, M. A. (2019). The ACCOuNT Consortium: A Model for the Discovery, Translation, and Implementation of Precision Medicine in African Americans. Clinical and Translational Science. https://doi.org/10.1111/cts.12608
- Hernandez, W., Gamazon, E. R., Smithberger, E., O’Brien, T. J., Harralson, A. F., Tuck, M., Barbour, A., Kittles, R. A., Cavallari, L. H., … Perera, M. A. (2016). Novel genetic predictors of venous thromboembolism risk in African Americans. Blood, 127(15), 1923-9.