gene sequencing

‘We can’t move fast enough’: Leukemia specialist determined to find cures

Driven by a sense of urgency, Pamela Becker, M.D., Ph.D., believes uncovering and targeting genetic mutations may hold the key to defeating blood cancers

Physician-scientist Pamela Becker, M.D., Ph.D., isn’t satisfied with today’s outcomes for people facing advanced blood cancers. And she has a vision for how to turn it around.

Pamela Becker M.D., Ph.D.
Pamela Becker, M.D., Ph.D.

“We have to do better to improve patient mortality from acute leukemia, and I can’t spend enough hours trying to change that,” said Becker, who recently joined City of Hope as a professor in the Department of Hematology & Hematopoietic Cell Transplantation. “I want to change the entire paradigm.”

The precision medicine expert aims to meet cancer on its own terms, in all its complexities. That means going beyond identifying a single mutation and prescribing a protocol with evidence of success against it.

Since 2009, Becker has been developing a test that profiles cancer cells along multiple dimensions and quickly matches the disease up against an exhaustive battery of potential treatments, in search of just the right therapy for each individual patient.

'There must be some way to find the Death Star embedded in every patient’s cancer.'
Pamela Becker, M.D., Ph.D.

Her investigations key on an important concept: clonal evolution. The very nature of cancer — out-of-control cell division — enables the disease to rapidly accrue mutations. There are more than 250 mutations seen in acute myeloid leukemia, on average about 13 per patient. But Becker often finds 10 times that many.

In Becker’s view, chasing mutations down one at a time isn’t the best recipe for success.

“Cancer is always mutating, and we’re not getting nearly as complicated as we need to,” she said. “Our treatments may kill off parts of the cancer, but then what emerges can be drug-resistant. What we’re looking to do is defeat clonal evolution.”

In service of that goal, Becker focuses on testing drugs and drug combinations in a custom panel for each diagnosis, and analyzing how the results correlate with mutation patterns or expressed genes. Her work delves into both the blueprint of genetics (from DNA sequencing) and how those genes are expressed (from RNA sequencing) and the cancer’s laboratory response to therapies — 170 drugs or combinations against leukemia and an equal number against multiple myeloma.

Motivated by Her Patients

The inspiration for this work derives from Becker’s patient care duties, in more ways than one. The struggles, and bravery, of the people she cares for are a major motivator.

“If you’re a physician-scientist, you’re a physician first,” she said. “Seeing what patients and their families suffer through in order to survive, that fuels the fire.”

At the same time, her clinical work points where her science needs to go. Observing the patterns in how certain mutations often appear together, and how others seem to be mutually exclusive, presents clues that inform her studies.

“You see the questions when you see the patients,” Becker said.

Her penchant for homing in on the fine details of disease — such as inspecting microscopic samples herself — goes back to the influence of her father, a prominent pathologist and forensic scientist in her native New Jersey. Occasionally accompanying him to work as a child, she had the chance to look at slides under the microscope herself (in a time of laxer lab rules). This kicked off an early fascination with the workings of life. She would follow that passion to Harvard University. 

As a member of the school’s first coed undergraduate class, she completed her bachelor’s in biochemistry in only three years. In Harvard’s joint health sciences and technology program with MIT, she was one of three women in the cohort of about 25 high-achievers looking to earn medical and research degrees at the same time. She endured plenty of hassling from her male classmates, but resolved to never let it get in her way.

“It felt like I had to struggle to pursue my dreams, even from the beginning,” Becker said. “I just kept galloping. I just kept racing.”

Facing Down Hurdles

That determination fuels her work today. The complexities of cancer aren’t the only obstacles she’s up against; she also must confront regulatory complications, health insurance restrictions and the logistical hurdles that go into funding clinical research. While Becker’s test earned a key certification in 2015 from the state of Washington, where she was previously on faculty at Fred Hutchinson Cancer Center, it has not yet received the same approval in California.

Still, there are bright spots. Becker savors the news of patients — people for whom nothing else worked — enjoying remission after using a regimen based on her test findings. A study she presented at the 2022 American Society of Hematology conference demonstrates that her strategy extended patients’ survival fourfold compared to other protocols deployed without her recommendation.

“To see those responses gives me hope,” Becker said. “It’s a remarkable thing to happen in anyone’s career.”

Finding kindred spirits at City of Hope played a substantial role in her choice to join the institution in 2022. She was drawn by supportive leaders and colleagues who share her interest in precision medicine, willingness to explore and sense of urgency.

“There are individuals here who get the concept, that there must be some way to find the Death Star embedded in every patient’s cancer,” she said. “I constantly feel like we can’t move fast enough. A lot of people here share that drive.”

Pictured above: Sequencing data from genomic analysis on left; a molecule on the right.