As an intern on a bone marrow transplant ward at the Glasgow Royal Infirmary, A. Keith Stewart, M.B., Ch.B., witnessed young adults struggling with the ruthlessness of often-fatal blood cancers and the vicious side effects of treatment. But he also saw the doctors' compassion, patients' resolve and the clear need for better therapies. This ignited his passion for fighting blood cancers.
The relentless pursuit of that passion underscores his leadership vision for the Center for Individualized Medicine. Here, Dr. Stewart shares his past experiences ... and his hopes for the future of personalized medicine.
How did you begin research in the area of genomics and blood cancers?
"Cancer is driven by genetic damage, and during my hematology training, I learned that determining the disrupted genetics behind the disease would be critically important. I went to do research in Boston, where we were sequencing single genes back when, in what now seems like the dark ages ... it was difficult. In the early 1990s, we read one gene a month, if we were lucky. Now, sequencing a person's entire set of more than 20,000 genes — known as the genome — takes only a day or two."
What role does the Center for Individualized Medicine play in advancing this research?
"The center has undergone a phenomenal period of growth and infrastructure building. The next phase of this exciting mission is to drive what we have built into the clinical practice of all of our physicians. I'd love to see each and every Mayo Clinic patient benefit from some form of individualized medicine in the next decade, no matter what stage of life they're at — whether they are well and want to stay that way, or sick and need our help."
How does the Center for Individualized Medicine directly impact patients?
"Patients come to Mayo Clinic with hope. They want Mayo Clinic to deliver solutions they might not be able to obtain elsewhere. It is a foregone conclusion going forward that these solutions will include genomics, which will revolutionize our ability to better quantify risk, diagnose disease early, select or discard an intervention, make treatments safer and drive down costs in the system. In other words offer real value to their care."
Will personalized or precision medicine affect all patients, even those who are healthy?
"With the price of sequencing dropping every year, it's inevitable that one day everybody will have their genome sequenced routinely. However, before that happens, it's my mission to make sure Mayo Clinic leads this rapidly evolving field to understand all the things the genome is telling us."
Can you explain what you wrote about the drug thalidomide in Science Magazine last year?
"The 55-year history of the drug thalidomide is Shakespearean in scope, awash in unintended consequences, tragedy, resilience, driven characters, and redemption. Its redemption has been in the resurgence as a therapy to treat hematologic malignancy. Thalidomide was originally marketed to pregnant women in the late 1950s and early '60s for insomnia and morning sickness. Soon it was discovered the drug caused terrible birth defects and it was taken off the market. Years after thalidomide was taken off the market, my research team and I discovered it was effective for treating certain blood cancers, though we had no idea why. But once we had the power to see how the drug interacts with our genomes, it all became clear."
What did you learn about the drug-genome interaction?
"The genomic research explained why thalidomide got to the market and was considered safe in the first place. We found that mice didn't have the right genes for the drug to work so it didn't expose them to the terrible birth defects seen in humans. It explained why the drug damaged pregnancies, why it activates the immune system, why cancer cells die after treatment and it explains who responds to the drug and who doesn't respond. It's all because of a drug-gene interaction."
How did you verify your findings?
"Based on this information, we studied a modern thalidomide derivative called lenalidomide. We paired it with two other well-known cancer fighting agents to treat 800 people with multiple myeloma. Nearly nine out of 10 patients responded to the treatment, which trumped a different regimen considered the standard of care. In just the past couple of years, we've contributed here at Mayo Clinic to understanding why these drugs work using genomic techniques. Mayo is now developing a test that we can use to determine whether you'll respond to these drugs. Now that's individualized medicine."
What is your hope for patients who have blood cancers today?
"Thirty years ago, survival in multiple myeloma averaged three years. Today survival has tripled and more and more patients are being cured without the side effects of older chemotherapy. I am confident that by using the genome to individualize treatments, match the right drugs to the right patient at the right time and discover new chinks in cancer's armor, the unmet needs and unnecessary suffering of many cancer patients will become no more than a bad memory."
Dr. Stewart is the Carlson and Nelson Endowed Director of the Center for Individualized Medicine. He is also recognized as the Vasek and Anna Maria Polak Professor of Cancer Research.