Personalized medicine in action
Michelle M. Ng
We are already beginning to see success stories of personalized medicine unfold as it becomes increasingly available as a treatment option for patients.
But how does personalized medicine work? What are researchers doing to “personalize” medicine?
There are a few different ways for doctors to use the genetic makeup of patients and their diseases to optimize treatment. While patients have been treated with a “one-size-fits-all” mentality in the past, it doesn’t make sense to care for a teenage boy the same way we would approach treating an elderly woman; and we now possess the tools that enable us to treat patients as individuals. These tools include huge databases that allow doctors access to biological information (such as the human genome sequence), new ways to categorize patients (e.g. via their genotype or cellular assays), and the technological power to compute large amounts of data.
If these resources are readily available, doctors can take advantage of them in several ways. In terms of intervention, we know that the presence of certain mutations (such as those in the BRCA1 and BRCA2 gene) indicate a higher likelihood for a woman to develop breast cancer. Screening women for this can lead to improved preventative care for those at risk and ideally stop the progression of the disease by its incipient stages.
Now say someone is already sick – personalized medicine still has tremendous potential to optimize the treatment process. One application is to take a close look at the patient’s genome before prescribing a certain drug or therapy. Gene expression profiling gives doctors a better idea going forward of what will and won’t work for a patient in order to avoid adverse drug reactions and/or treatment failure.
For instance, Abacavir is a medication used to treat HIV/AIDS. While well tolerated by over 90% of people, it can cause a serious hypersensitivity reaction in others. Antecedent tests for this negative reaction relied upon skin patches – an extra step that was not always accurate – until a strong link was discovered between hypersensitivity to Abacavir and the allele HLA-B*57:01. This led the FDA to recommend checking patients for the gene before they begin to take Abacavir. Now, by pre-screening individual patients, doctors use personalized medicine to determine which treatment (whether Abacavir or some other medication) they may safely and effectively prescribe.
Another personalized medicine application for treating cancer, in particular, involves patient-derived xenograft (PDX) cancer models, or mouse avatars. Once bits of a patient’s tumor are grafted onto identical, immunocompromised mice, each mouse receives a different type of treatment to see exactly how each option acts upon the patient’s individual form of cancer. The therapy that is most effective with shrinking the mouse’s tumor would then be administered to the patient. This works because the tumors in the mouse and patient are genetically identical, so what works on one tumor works effectively once again on the same tumor in the patient.
An example of this in action was recently published by The Sacramento Bee, which covered a story of The Jackson Laboratory’s PDX mice helping 77-year-old Gale Kilgore fight bladder cancer. The drug (cisplatin) that eventually shrunk her tumor initially made her feel sick – it was only cisplatin in conjunction with gemcitabine (which interferes with mitosis in cancerous cells) that is helping her battle Stage 4 cancer. Typically, Kilgore’s negative response to cisplatin would have been a sign to cross the drug off the list of possible treatment avenues. However, when a combination of the two medications surprisingly reduced the size of one of her mice’s tumor dramatically, Kilgore was put on the same medications with similar success to date.
In addition to cancer, personalized medicine has the potential to change our effectiveness in treating many other diseases, such as Alzheimer’s, which might also be linked to mutations in DNA, and diabetes, whose chances of developing might be lessened by those most at risk making crucial lifestyle changes.