Targeting cancer, precisely

At the vanguard of next-generation precision medicine, Dr. Pamela Becker’s work through the Institute for Stem Cell and Regenerative Medicine is taking aim at cancer.

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Dr. Pamela Becker is all
too familiar with long odds.

The UW Medicine hematologist who specializes in blood cancer 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.

For AML patients over 65 years old, the survival rate drops to an abysmal 10 percent. Even with treatment, these patients survive less than a year on average.

"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.

PAMELA BECKER

M.D., Ph.D.

Professor of Medicine,
Division of Hematology

1:09 / play interview

What I focus on is how patients with acute myeloid leukemia … why they don’t respond to the current treatment options. And what we learned was that when we tested individual patient samples against a large panel of different drug agents and drug combinations that each patient had a different response to every single drug. So that no patient looked like any other patient.

We have unique resources here at the Institute for Stem Cell and Regenerative Medicine. We have the Quellos High-throughput Core facility which can do screening of individual patient cell samples to look for the best drug for an individual patient.

So we’re constantly testing new compounds, new combinations of compounds, and trying to improve our therapy.

So patients who have multiple relapses with their acute leukemia, and have had many prior therapies, typically their survival is quite limited. Perhaps less than even three months. And we’ve been able to extend survival. We now have many patients who’ve survived several months, or even a year after they’ve relapsed after a transplant for acute myeloid leukemia, and I think that this ability to keep treating and treating, and having patients survive longer is a consequence of this therapy so far.

And the hope of all of this is that eventually someday we may be able to do much better.

The art of empathy

Though Dr. Becker often thinks of cancer on a scientific level, there’s a point where the science of beating cancer meets the art of empathy. Her mother, who has survived thyroid and breast cancer, was recently diagnosed with lung cancer.

“I appreciate what it takes to go through all the diagnostic procedures, the treatments, the side effects, the stresses,” Dr. Becker says. “Now, I have an incredible, renewed appreciation for how devastating this is. Not only to the patients, but to their families and friends. I’m always trying to think of how we can make it better, do better — how we can restore quality of life and prolong survival.”

At ISCRM, a collaborative institute at the forefront of biomedical research, experts take on the most daunting diseases of today — from Alzheimer’s to diabetes to cancer — 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?”

These are the questions she is working to address in her precision medicine approach to cancer treatment, and she’s already making significant progress.

Crucial to her research has been ISCRM’s Quellos High-throughput Screening Core. Housed in a quiet lab at UW Medicine at South Lake Union, the facility’s automated machines can test high volumes of drug compounds at different concentrations, finding 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. ’84, 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. 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.” In a different trial using the Quellos Core, for example, a leukemia patient responded well to a drug normally used to treat lung cancer.

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.

There’s Lawrence Loeb, M.D., Ph.D., a biochemist and pathologist who’s studying clones and sub-clones of cancer cells that proliferate during a relapse. There’s Ka Yee Yeung-Rhee, Ph.D., a big-data expert who is looking for statistical patterns in cancer patients’ genetic mutations and the drugs they respond to. And there’s Su-In Lee, Ph.D., a computational biologist and engineer who works to identify genes that lead to specific drug sensitivity.

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.”

Chuck Murry

M.D., Ph.D.

Joint Professor, Pathology, Cardiology and Bioengineering Interim Director, Institute for Stem Cell and Regenerative Medicine Co-Director, Center for Cardiovascular Biology

AT THE HEART OF THE CURE

Chuck Murry shows off a tiny white scar on his forearm, left over from a biopsy. The cells he had removed are still alive, but they’re no longer skin cells.

“I had my own skin turned into stem cells,” he says. “It’s now three-dimensional heart muscle that’s beating in a dish.”

This literally transformative work isn’t a mere exercise. Dr. Murry and researchers in his lab are using stem cells to grow and test heart tissue with the aim of repairing damaged hearts. “And once we get this sorted out for the heart,” he says, “we’d like to do it for other organs.”

ISCRM BY THE NUMBERS

  • UW faculty: 117
  • Patents issued: 398
  • Companies started: 20
  • Publications by core faculty in 2015–16: 142

At ISCRM, researchers like Dr. Murry are pioneering ways to derive stem cells from skin, blood and even urine samples. These powerful cells have the astounding potential to create next-generation therapies for maladies like heart disease, Alzheimer’s, rheumatoid arthritis, vision loss and cancer.

ISCRM was founded by Dr. Murry, UW Medicine pharmacologist Randall Moon, Ph.D., and UW Medicine hematologist Tony Blau, M.D., in 2006. Dr. Murry describes the institute as the glue that promotes synergy among all the different types of expertise needed — including developmental biology, imaging, pathology and much more — to advance our knowledge.

And, in just a decade, doctors at ISCRM have made significant progress — from developing a potential gene therapy for muscular dystrophy, to using patient-specific stem cells to find treatments for a condition that affects vision.

The future of ISCRM holds great possibility, and its success to date has hinged upon generous philanthropic support.

“It couldn’t be simpler,” says Dr. Murry. “Without the vision and generosity of our benefactors, there would be no stem cell institute.”

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