Oregon Health & Science University researchers have identified a drug duo that could help people with acute myeloid leukemia overcome treatment resistance. By pairing a standard leukemia drug with a breast cancer medicine, the team saw stronger, longer-lasting anti-cancer effects in lab and animal studies.
A breast cancer drug already on the market may help one of the deadliest forms of blood cancer respond better to treatment, according to new research from Oregon Health & Science University.
In lab dishes and mouse models, OHSU scientists found that combining venetoclax, a standard drug for acute myeloid leukemia, or AML, with palbociclib, a breast cancer medicine, produced more powerful and longer-lasting anti-leukemia effects than venetoclax alone. The work, published in the journal Cell Reports Medicine, suggests a new way to tackle one of the biggest obstacles in AML care: drug resistance.
AML is one of the most common and aggressive types of leukemia in adults. More than 20,000 Americans are diagnosed each year, and despite recent advances, long-term survival remains low.
Venetoclax, used with another drug called azacitidine, has quickly become a frontline option for many patients since it was approved by the Food and Drug Administration in 2019. It can shrink leukemia cells and improve quality of life, especially for older adults who cannot tolerate intensive chemotherapy.
But the benefits often do not last.
“Unfortunately, almost everyone will eventually have drug resistance,” corresponding author Jeffrey Tyner, a professor of cell, developmental and cancer biology in the OHSU School of Medicine and the Knight Cancer Institute, said in a news release. “This regimen has improved initial response rates and quality of life, but the five-year survival rate for AML is still only about 25% to 40%. We have a lot of work to do.”
To search for better options, the OHSU team tested 25 different drug combinations on more than 300 AML patient samples. They were looking for partners that could boost venetoclax and help leukemia cells stay sensitive to treatment.
“Of the 25 drug combinations tested, venetoclax plus palbociclib was the most effective. That really motivated us to dig deeper into why it works so well — and why it appears to overcome resistance seen with current therapy,” added lead author Melissa Stewart, a research assistant professor in the OHSU School of Medicine and Knight Cancer Institute.
Palbociclib is a type of targeted therapy known as a CDK4/6 inhibitor. It is currently approved for certain types of breast cancer, where it works by slowing down how quickly cancer cells move through the cell cycle and divide.
The idea of using a breast cancer drug in leukemia might sound surprising, but the researchers say it reflects a growing understanding that different cancers can share the same biological weak spots.
“Some might ask why a breast cancer drug would work in AML,” Tyner added. “But biology can be shared across very different cancers. This is a great example of why keeping an open mind matters and following the data where it leads.”
The team’s experiments showed that when AML cells are exposed to venetoclax alone, they try to adapt by ramping up protein production. That shift in how cells make proteins appears to help them survive and eventually resist the drug.
Adding palbociclib blocked this survival strategy. By interfering with the cell cycle and the machinery that controls protein production, palbociclib helped shut down multiple pathways leukemia cells use to escape venetoclax.
“Patient samples that responded strongly to the combination showed clear downregulation of genes involved in protein synthesis,” added Stewart. “This was a big clue.”
To probe the biology further, the researchers used a genome-wide CRISPR screen, a powerful tool that can systematically turn off genes across the entire genome. They found that venetoclax alone became more effective when genes tied to protein production were lost. The combination therapy, however, did not depend on that same vulnerability, suggesting the two drugs work together to close off several escape routes at once.
The team then moved to animal studies, using mouse models implanted with human AML cells that carry genetic mutations known to make venetoclax less effective.
“In this model, venetoclax alone didn’t extend survival at all — just as we’d expect based on the genetics,” Stewart added. “But with the combination, the majority of mice lived 11 to 12 months. In fact, one mouse was still alive when the study ended.”
Those preclinical results do not guarantee the same benefit in people, but they provide a strong rationale to move toward clinical testing, the researchers said.
The project also has a deeply personal dimension for Stewart.
“I’m a breast cancer survivor and was treated here at OHSU, so I know what it’s like to be a cancer patient,” she said. “The hope that research and clinical trials can bring — that’s what motivates me. Working on AML gave me a way to contribute.”
The new study builds on the national Beat AML 1.0 program, a large effort aimed at transforming AML treatment by matching patients with therapies based on the genetic and molecular features of their disease. Tyner, a co-leader of that initiative, said the venetoclax–palbociclib pairing emerged from those data.
“This combination was nominated from the Beat AML data, and Dr. Stewart validated that prediction, showing not only that it works, but why,” Tyner added.
Because palbociclib and several similar CDK4/6 inhibitors are already approved for breast cancer, they have known safety profiles, which can sometimes speed the path to clinical trials in new settings. The team is already exploring other drugs in the same class to broaden future options for patients, according to Stewart.
The researchers emphasize that the venetoclax–palbociclib combination has not yet been tested in people with AML, and patients should not expect immediate changes to standard care. Any new regimen will need to go through carefully designed clinical trials to assess safety, dosing and effectiveness.
Even so, the team is optimistic about what the early data suggest.
“We haven’t tested it in patients yet, but based on everything we’ve seen, our prediction is that this combination would mitigate most known resistance mechanisms to the current standard therapy,” added Tyner. “Making it a clinical reality will take work, but this is exactly why we do what we do.”
If future trials confirm the findings, the approach could offer new hope to people facing a cancer that often returns despite initial treatment. More broadly, the study highlights how rethinking existing drugs and looking across cancer types can uncover unexpected strategies against some of the toughest diseases.