You can customize your music playlist. You can customize your ringtone, your restaurant order, your credit card image, your Facebook page, and even your Sharpie (it’s true – if you want a lime green Sharpie with paw prints and your dog’s birthday on it, you can get it). But what if your medical care could be customized, your treatments tailored just to you – and not in some sort of touchy-feely, I’d-like-a-room-with-a-window-and-pink-sheets sort of way, but genetically? The idea is called personalized medicine, and it’s a potentially transformational concept that may improve outcomes for patients with cancer and other diseases.
When the Human Genome Project began, researchers hoped to find out which genes were responsible for causing various diseases. What they found was more complicated. While some diseases, such as sickle cell anemia and Huntington’s, are caused by a single gene mutation, many others, including cancer, seem to be the result of factors that cross multiple genes. By looking at a person’s entire genome, researchers hope to better understand these diseases and their potential treatments.
The Promise of Personalized Medicine
The premise behind personalized medicine is fairly simple: people are different from one another in terms of lifestyle, environment, and genetics, and some of these differences affect health. One person’s DNA, for example, might increase their likelihood of developing breast cancer or heart disease. A person’s stress level, diet, or exposure to toxins might reduce or increase this likelihood. Genes can also play a role in whether or not a certain treatment is effective for a specific person. Personalized medicine takes these factors into account when seeking to prevent and treat diseases. There is also the hope that personalized medicine might teach doctors more about who is likely to experience side effects from specific drugs.
How Futuristic Is It?
According to Dr. Francis Collins, director of the National Institutes of Health, personalization is the future of medicine, but that doesn’t mean it is years away. In fact, the Personalized Medicine Coalition (PMC) points out that some personalized treatments are already available, and researchers are currently working on many more.
For example, Dr. Brad Carter (82) of the H. Lee Moffitt Cancer Center in Florida noted that in about 20 to 30 percent of breast cancer cases, a specific protein, called HER-2, is over-produced. A drug called Herceptin targets HER-2 positive breast cancer cells and has proven to be very effective. Herceptin doesn’t work as well for patients whose breast cancer is HER-2 negative, so its best use is as a personalized treatment for those with HER-2 positive breast cancer.
Carter calls treatments like Herceptin “smart bombs” as opposed to “nuclear bombs” like chemotherapy, meaning that they more directly attack cancer cells and have fewer side effects on normal cells.
If a healthy person’s genomic scan indicated a higher than average risk for a particular disease or condition, the person might be able to benefit from strategies aimed at preventing the disease or controlling it. This might mean undergoing more frequent screenings or even taking preventive medication. For example, in the case of breast cancer, the drug tamoxifen has been shown to lower risk among women with a genetic predisposition for the disease. Different diet, exercise, or other lifestyle choices might also help the person.
(Of course, compliance will still depend on the patient. A recent study indicated that many people do not want to take preventative medications like tamoxifen because of a fear of side effects.)
Despite the personalized option Herceptin offers to some breast cancer patients, Carter notes that chemotherapy is still the recommended treatment for most stage two breast cancer patients.
“Without treatment, patients with stage two breast cancer have a 30 percent risk of the cancer spreading to solid organs,” he said. “Chemotherapy only reduces the risk to 15 percent. Right now, we don’t know who the 15 of each 100 patients are.”
The goal is to figure that out so that treatment options can be improved and given to those who need them. Those whose cancer wouldn’t progress anyway might be spared the side effects of unnecessary chemotherapy and be treated only with surgery, for example.
The possibility of preventing unnecessary treatments is one that appeals to Dr. Robin (Reber) Leach (78) of the University of Texas Health Science Center as well. Leach, who studies the genetics of complex diseases, has done considerable work on prostate cancer. She notes that about 20 percent of prostate cancer patients will have their disease progress without treatment, but that means 80 percent won’t.
“We may be over-treating,” she said. “For those with low risk, it may make more sense to do active surveillance of the disease than to treat with surgery or radiation that may not be necessary.
In addition to providing better advice to patients as to which treatments to choose, genomics may also help with finding better treatments in the first place.
According to the PMC, “The expanded use of biomarkers – biological molecules that indicate a particular disease state – could result in more focused and targeted drug development.”
Moffitt, for example, is partnering with pharmaceutical company Merck to obtain the genomic profiles of various cancers. According to Carter, so far, they have profiled more than 10,000 tumors and are now comparing treatments and outcomes.
Ethical and Policy Questions
Although the promise of personalized medicine is great, there are many questions that remain to be answered.
Questions about Cost
If a drug will help only a few thousand people and millions of dollars will be spent to discover and produce it, should a pharmaceutical company still make it? If a drug worked better, would you pay more for it? Would you pay more if it meant someone else’s drug would work better?
In 1983, the Orphan Drug Act was passed in order to provide incentives for pharmaceutical companies to develop drugs that treated diseases from which 200,000 or fewer Americans suffer. According to Dr. Mark Jameson (92) of the University of Virginia Health System, personalized medicine is unlikely to suddenly render each type of cancer an orphan disease. It’s also unlikely to split cancer patients into so many subgroups that treatments will not help large numbers of people. While Jameson recognizes that cancer is not “a” disease, and that within specific types of cancer there are often many variations, he notes that there are common biological mechanisms that drive the growth of cancer cells.
The head and neck squamous cell carcinomas that Jameson treats can be caused by smoking, alcohol use, and human papillomavirus (HPV) and can exhibit substantial variability.
“In the past, squamous cell carcinoma patients were typically male smokers. Now, there are more HPV-related cases, and both genders are affected. It’s not one cancer. It can be triggered by different genetic mishaps. There is a lot of heterogeneity,” he said.
But he went on to stress that many of these triggers are common to other cancer types. For example, the same HPV strains that can cause head and neck cancer are responsible for most cervical cancer, and the HER-2 protein that is involved in some breast cancers also plays a role in some head and neck cancers.
Jameson believes that personalized drug combinations for head and neck squamous cell carcinoma will involve a handful of medications selected from perhaps 12 – 20 options, but “probably not 100.” Thus, while there will likely be some fragmentation in the market for squamous cell carcinoma drugs, “you probably won’t have to build a drug for three people,” he joked.
More seriously, Jameson emphasized that it is likely that drugs targeted to a certain genetic variation of one type of cancer will also work to treat other cancers, particularly when applied in combination. This is the case with the landmark drug, Gleevec, which has revolutionized treatment for chronic myeloid leukemia. Gleevec can also be used to treat nine or so other kinds of cancer.
None of this means that questions about cost don’t matter. It does mean that researchers and pharmaceutical companies are aware of the issues and are working to make personalized medicine feasible.
Questions about Patient Rights and Privacy
If you could find out whether you had a genetically higher risk of developing cancer, should you be required to tell your insurance company? Should they be required to cover you anyway? What if genomic testing suggests a drug isn’t likely to work for you, but you still want to try it? Should your insurance company cover it? If certain health risks become associated with certain sub-groups of the population, will these groups be stigmatized?
These are serious questions that the PMC is attempting to bring to policymakers’ attention. In order for consumers to buy into the concept of personalized medicine and genomic testing, they need to feel that their rights and privacy will be protected. This, too, is an area of which personalized medicine advocates are keenly aware. National organizations and universities are collaborating at a number of colloquia and conferences to discuss these questions and how to handle them.
While the issues surrounding personalized medicine are thorny, they are worth tackling. The hope genomics offers to those with cancer and other genetic diseases – as well as to those who may be susceptible to them – is too promising to be ignored. In Francis Collins’ book The Language of Life: DNA and the Revolution in Personalized Medicine, there is a character for whom two possible futures are envisioned, one where she receives the benefits of personalized medicine and one where she doesn’t. The difference is stark – her life span more than doubles when her genomic profile is taken into account. The character’s name? Hope.