Find Your Best Dose with DNA-Driven Prescriptions
Genetic and genomic testing both helping to pinpoint better medical care
We all know someone who is either highly sensitive to medication or can never seem to find anything that works. What seems like a random trait is actually explained in our genes. DNA is our blueprint of life, and as technology improves, understanding what genes tell us is leading the way to better pharmaceutical choices and precision medical treatments.
Months ago, a family member's physician prescribed her a new antidepressant based on the results of a DNA swab taken from inside of her cheek because the medication she was taking was no longer working. The new one, guided by the DNA results, did.
To say I was impressed was an understatement, and a quest to learn more about this novel realm of science sent me down the proverbial rabbit hole to understand how both genetic and genomic testing can customize medical treatment from depression to cancer.
Benefits and Challenges
My first stop was pharmacogenetics, or how genetic variants within each individual affect the efficacy of a drug. When appropriate, a physician takes a DNA sample, whether through a cheek swab or blood sample, and the lab looks for specific genetic markers that can tell them the best choice. This is why one drug works beautifully for one person but does little to nothing for another.
"The gene affects how the drug is metabolized," explains Jerry Mitchell, M.D., a medical oncologist and medical director of Precision Genomics Oncology at Foundation Medicine.
As one example, according to a report by the Cleveland Clinic, if you have a variant of the SLCO1B1 gene, you are most likely to experience muscle pain and weakness when you take a statin drug for high cholesterol. This explains why many people suffer this often intensely distressing side effect while others don't.
[But] it does not guarantee that a particular medication is the answer, and knowing how a person's DNA breaks down one drug doesn't mean it'll work in combination with other medicines.
The beauty of pharmacogenetics is that instead of relying on a trial-and-error approach to matching the proper medication for a person, testing DNA offers an opportunity for more precise medical decisions.
Yet, even with positive potential, it is far from perfect, and there is still work to refine the process. Despite a more definitive understanding of an individual's genes, it does not guarantee that a particular medication is the answer, and knowing how a person's DNA breaks down one drug doesn't mean it'll work in combination with other medicines.
The other challenge can be cost. Some insurance plans cover pharmacogenetics, but not all, because they are not considered medically necessary. Yet, as with other treatments that were not initially classified in the same light, a growing interest in this science might change its status.
Cancer Treatments
While pharmacogenetics efficacy has enormous benefits for many people when it comes to choosing the right medication, researchers are also looking for more effective means of improving cancer treatments and their subsequent outcomes. In this case, while pharmacogenetics tailors treatment based on a person's specific genetic markers, genomic testing focuses on the cancer's genetic makeup. This allows physicians to determine what therapy will target each patient's unique cancer.
"We don't sequence the individual's genes; we sequence what's in the cancer," Mitchell explains. "The cancer has a whole different set of genes than what you see in the body."
Tracey Davison in Inman, South Carolina, says she remembered hearing about genomic testing about eight years ago when she was initially diagnosed with non-Hodgkins lymphoma. "The medical field was doing it, but the doctors were not really offering it. I don't think it was the typical protocol at that point."
Not one to automatically jump on the chemotherapy course of action, she says, "I tried a lot of the natural therapies beforehand. I even completed a 28-day water fast. They built up my system, which was great." But they did not shrink the cancer. In reality, the tumor eventually increased.
"About two years ago, my doctor said, 'Don't wait another year," says Davison. Unfortunately, she and her husband were looking at roughly a $300,000 medical bill, even with insurance.
Davison learned more about various options, including genomic profiling of the cancer. She says, "It will tell you the most effective chemo treatments and other anti-cancer drugs."
Once her test was completed, Davison says, "It gave me a list of chemotherapies that would work." Most importantly, they discovered that she had a drug-inhibitor gene (the MDRI, multi-drug resistance gene), so she needed an inhibitor-blocking medication.
"This lets the drug get in, so it will actually work."
"This lets the drug get in, so it will actually work," she says. This gave her oncologist the tools needed to target the cancer more effectively.
Besides bringing aboard the technological marvel of genomic profiling to determine the specific chemotherapy, Davison continued to work closely with a trusted naturopathic physician who provided additional support for her system with vitamin C infusions and carefully chosen supplements.
After three chemo treatments and monoclonal antibodies, she continues, "My most recent scan was in September (2024) and it showed full remission. Other than hair loss, I didn't have any side effects."
She appreciates the technology that allows her to make a judgment call on her treatment. "I have a great oncologist," she says, but she reminds patients that they have to be their own advocates. This is especially true when it comes to genomic profiling, which might be new information to some physicians.
History of the Technology
While this innovation is cutting edge, its foundation was formed in the 1960s with chronic myeloid leukemia (CML), which Mitchell describes as the poster child of how this technology works. Scientists discovered that people who developed this slow-growing bone cancer had an abnormal chromosome, called the Philadelphia chromosome, in their blood. Although researchers understood the reason behind the condition, it was not until the late 1990s that they developed a molecular means of shutting down the signals and controlling the disease.
"The science changes every day," Mitchell notes. "We are looking at how the tumor reacts with the drugs."
Unlike pharmacogenetics, genomic profiling involves DNA sequencing of cancer cells. Mitchell points out that cancer happens in the genes because certain genes might split through environmental or inherited conditions, and when they rejoin, cancer is created.
"The science changes every day."
Mitchell explains, "Tumors shed DNA in the bloodstream." Because of this, many times, the cancer's DNA can be detected via a high-quality blood test, but not all of them. He continues, "Some cancers do not shed DNA into the bloodstream at all, and sometimes, those cancers that do shed are at an early stage, and this doesn't happen. At Foundation Medicine, we developed a very sensitive way to measure the cancer's DNA."
This information forms a targeted treatment plan with the patient's oncology team. Mitchell stresses the importance of information and advocacy because delving into the realm of genomic technology, whether on the pharmacological or oncological level, is not a familiar space for all physicians. This is partly because technology is changing so rapidly.
"The only way we would know if a cancer treatment was working for the past 50 years was to take a physical image (of it)."
"None of the technology existed when many physicians, including myself, were in training," he says. To educate patients and physicians, "We have a lot of interaction with patient advocacy groups."
Looking Ahead
While they are not at this point, there are exciting possibilities for the future. Mitchell says, "The only way we would know if a cancer treatment was working for the past 50 years was to take a physical image (of it)." If it looks bigger, we assume the cancer is spreading, but this is not always true."
"Where the next need is to be able to better predict the response to treatment based upon what happened in the DNA," he says. This way, he says, they can see the DNA marker changes and can prognosticate what is happening.
"Where the next need is to be able to better predict the response to treatment based upon what happened in the DNA."
"But what we need is something that is predictive," he continues, to understand how a tumor will respond in the long term.
"If you can track the changes for a specific molecule, you can stop the therapy, and the cancer wouldn't come back half of the time," he says. If, although hopefully when, this is a reality, it would allow physicians to cease a medication when the indicators are positive and start it again, if necessary. "This will help us not overtreat as many people."
Mapping these genomic codes, whether to determine the efficacy of medications on a particular individual or how best to shut down a cancer's progress, provides an almost magical bit of information that doctors and patients need to experience better outcomes.
