By Jon Parham
In just a couple decades, the UAMS Myeloma Institute of Research and Therapy built an international reputation for dramatically improved survival rates boosted by its translational research effort.
In late 2008, the institute started one of the first – if not the first – clinical trial for multiple myeloma where treatment of each patient with the cancer was determined by the disease’s genetic fingerprint of 70 genes. Early indications show personalizing the treatment plan for each patient improves the response rate – especially for those roughly 85 percent of patients with what the institute now calls the standard version of the disease.
“The ongoing successful response to treatment in standard-risk myeloma offers an enormous paradigm shift in multiple myeloma,” said Bart Barlogie, M.D., Ph.D., Myeloma Institute director. “We continue to move from what was considered a no-cure situation to having a cure.”
Now all new myeloma patients receive a gene expression profile, and based on genetic tests, a course of treatment is proposed. Institute scientists continue to refine the genetic profiling of the disease, allowing development of even more customized treatment plans, said Frits van Rhee, M.D., Ph.D., director of clinical research at the institute.
“The ultimate aim is to cure multiple myeloma and we do that through better individual therapy to improve outcomes of patients regardless of the type of the disease that they have,” he said. »
The Myeloma Institute’s success at personalized medicine may offer a glimpse at the future of medicine, where treatment of conditions from cancer to high blood pressure, and from depression to age-related effects on the heart, will be driven by an individual’s genetic makeup. “A generation or two from now, personalized medicine will be routine and we need to be leading
the transformation,” said G. Richard Smith, M.D., director of the UAMS Psychiatric Research Institute and a proponent of establishing a center for personalized medicine at UAMS.
Such a center would bring focus to early, scattered research efforts on the campus and build infrastructure that would unify research, clinical and academic resources toward that future.
Beginning to unlock the possibilities of the body’s genetic code has led to high-profile successes in personalized medicine.
Understanding that cancer is not one disease but – at the genetic level – many different diseases proved a boost to the idea of personalized medicine. “All lung cancer is not the same and each type has to be treated differently, so there is never going to be one single cure for cancer,” said Peter Emanuel, M.D., director of the UAMS Winthrop P. Rockefeller Cancer Institute.
More personalized medicine marks a shift away from medicine based on statistical knowledge of what treatment is successful with most patients. If clinicians knew that 7 to 8 percent of patients with a specific tumor genetic profile responded better to a certain treatment, for example, then outcomes significantly improve for those patients. But if they treated all patients that way, it would look like a failure because there’d only be a 7 percent response rate, Emanuel said.
“Personalized medicine is driving toward one patient, one answer,” said Jennifer Hunt, M.D., chairman of the Department of Pathology in the UAMS College of Medicine. “We understand now that knowledge of a cancer tumor’s genetics can be a predictor of how the disease will progress.”
It’s not just cancer
Genetically inherited disorders usually become manifest before age 60. After age 60, the development of disease is more dependent on the body’s interactions with the environment. These may include lifestyle, nutrition and exposure to substances such as cigarette smoke, toxic chemicals and radiation, said Jeanne Wei, M.D., Ph.D., director of the UAMS Donald W. Reynolds Institute on Aging.
That does not mean, however, that tantalizing possibilities don’t exist for personalized medicine in seniors. Researchers at the Institute on Aging have shown that epigenetics, or altered programs of gene expression, in the heart could make it more vulnerable to stress – and thus contribute to increased morbidity and mortality.
Their work suggests that changes in gene expression, or the way a gene is regulated in a cell, could also potentially make an older heart stronger. It could therefore, be a matter of figuring out how one’s genetic code sends messages that modulates how the cells react to stress – before scientists can learn to influence the processes themselves.
“Personalized medicine means that we can do everything possible to enhance or maximize the health in an individual,” Wei said. “Everyone will be different, and if we can understand and alter the patterns of gene expression in a coordinated way, it will help improve outcomes for our patients.”
How a range of medications for treatment of conditions from depression to high blood pressure are metabolized in the body is regulated by a set of enzymes controlled by a number of genes. Some patients cannot metabolize or some metabolize too fast, possibly making the medication become toxic or ineffective. Again, knowledge of an individual’s genetic makeup will make treatment more effective by giving clinicians information for choosing the medicine that will work best.
Instead of generic practice guidelines, physicians will be guided by genetic data on specific patients. But there’s a key challenge to such personalized medicine, said William Hogan, M.D., director of the Division of Biomedical Informatics in the College of Medicine. The current electronic medical record has no place for genetic information.
“As we have learned, different genes have influence over disease response and disease progression. The question then is how do we get that information into the electronic medical record in a way that a physician can use it?” Hogan said.
Some of the building blocks for more personalized medicine exist already at UAMS or are coming together.
Two new research floors funded through the federal stimulus act recently opened in the Cancer Institute. One of the newly recruited researchers there works with proteomics, which could impact personalized medicine as the function and processes controlled by chemical proteins in the body are better understood.
Projects in population genetics demonstrate the potential personalized medicine has for population groups. More than 22,000 women to date have donated samples of saliva as part of the Spit for the Cure study at UAMS, building a database of genetic information for breast cancer researchers seeking clues related to cancer risk and treatment.
A research data warehouse established in 2011 is building clinical information that could serve as a resource for researchers looking to turn epidemiological information into scientific investigation. Adding genetic profiles to patient data makes the warehouse even more powerful.
A center for personalized medicine could be the next step. Hunt, Smith and others believe UAMS is well positioned to have an effective program, even in a smaller state without the resources of larger academic health centers.
“It may be a leap of faith to some extent because the return on investment might not be immediate,” Hunt said. “But, if we develop a test that can predict that a treatment will not work with certain patients based on the genetic profile, then we will save money and protect patients from unnecessary, wasted therapy.”
It is a commitment to more comprehensive care and fitting for UAMS in its role as the state’s only academic health center. A center would allow coordination of resources behind initiatives with the best combination of expertise and promise for results, Smith said. It will put support behind acquisition of needed equipment for analysis and begin integrating education about personalized medicine into academic curriculums.
“When I started using genetic information for dosing and would get the pharmacogenetic information,” Smith said, “it would probably take about an hour and a half of a nurse’s time and an hour of my time per patient to review the information and results, then prepare a plan for acting on that information and explaining it to the patient.”
Faster computer analysis and interpretation has sped up the process, he said, but it highlights system changes required for wider use of personalized medicine.
“We are on the cusp of a genomics revolution in medicine,” Smith said. “This means curriculum changes, clinical practice changes, research changes and a method for retraining the current workforce. Our whole system will change.”