Dr. Pamela Becker, is all too familiar with long odds.
Becker, an M.D., Ph.D. hematologist with UW Medicine, specializes in blood cancer. She often sees patients with diseases like acute myeloid leukemia (AML), a fast-progressing cancer that takes the lives of three out of every four patients within five years.
“We have to do better,” says Dr. Becker. “And if we get it figured out for leukemia, we can figure it out for other cancers, too.”
That’s why she’s working with UW Medicine's Institute for Stem Cell and Regenerative Medicine (ISCRM) to pioneer groundbreaking treatments — and turn the odds in her patients’ favor.
At ISCRM, a collaborative institute at the forefront of biomedical research, experts take on the most daunting diseases of today, using cutting-edge technology and research to support promising clinical trials.
In Dr. Becker’s case, the path from research to next-generation therapies begins by rethinking how the cancers she studies are currently treated.
Typically, she explains, patients get the same treatment for leukemia: two types of chemotherapy drugs. The drug programs are intensive. They’re costly. They’re toxic, with life-threatening complications and severe side effects. And for a third of those patients, they don’t help at all.
“But what if there weren’t just two types of drugs?” asks Dr. Becker. “And what if the drugs we used to fight AML were selected based on each patient’s unique biology?”
Crucial to her research has been an facility housed in a quiet lab at UW Medicine at South Lake Union. Called the Quellos High-throughput Screening Core, the ISCRM facility runs plate after plate of patient samples through automated machines. By testing patient samples against high volumes of drug compounds at different concentrations, scientists are able to find the best matches for each person’s cancer. And they can do so quickly, giving Dr. Becker and her patients an edge in the race against time.
In a recent clinical trial, Dr. Becker’s team screened cancer cells from several late-stage AML patients against more than 160 drug compounds.
Timothy Martins, Ph.D., director and principal scientist of the Quellos Core, recalls that about 25 years ago, it would take him over a month to test just 20 drug compounds. “Now,” he marvels, “it only takes five days to test 160 or more compounds.
“The faster turnaround time is much better for these patients,” Martins explains. “Treatment can begin much sooner, rather than waiting weeks for the results of other tests.”
Once the data were in, Dr. Becker was able to treat her patients with the drugs the screenings showed would be most effective. The results were promising: 13 out of the 14 patients treated with drugs suggested by the study showed a significant drop in leukemia cells, responding to drugs that doctors wouldn’t necessarily have thought to recommend.
“I can’t yet pick the home run,” Dr. Becker says. “And I can only find out afterward if we were successful, but the results are often surprising.”
But it’s not as simple as identifying a drug that works and sticking with it. A hallmark of cancer is its genetic instability, and cells that survive a treatment regimen often mutate and proliferate. They may grow drug-resistant, making a second round of treatment much less effective, or they may turn into something new.
And there’s another challenge: “When we say someone has a cancer, they don’t,” explains Dr. Becker. “They have a group of cancers.”
In other words, cells from one part of a tumor might have a different genetic makeup than cells from another part. If a drug kills the cells from biopsy A, the cells from biopsy B could live on.
With cancer’s manifold complexities in mind, Dr. Becker is working with other UW faculty to understand what happens when patients relapse: Which cancer cells survive, and why? What are their weaknesses? And what can we learn about new mutations and gene expression that will help current patients — and save lives in the future?
“We’re looking at all these different dimensions,” says Dr. Becker, whose approach to precision medicine is one of the most advanced in the world. “With a more global approach, we’re trying to find new points of vulnerability.”
There is much work to be done to identify and exploit weaknesses in each cancer’s armor, but right now, Dr. Becker’s clinical trials are giving her patients the gifts of time — whether it is months or years — and hope.
“I look forward to a day when 100 percent of our AML patients live for five years, rather than just 25 percent,” says Dr. Becker. “A future where we don’t ever have to lose a person to this disease again.”
Learn more about how UW is changing the future of cancer treatment.