Researchers at Oregon Health & Science University have made a significant breakthrough in the fight against acute myeloid leukaemia (AML), discovering that combining a standard AML treatment with a breast cancer drug dramatically improves treatment outcomes and overcomes a major obstacle facing patients today.
The groundbreaking study, published in Cell Reports Medicine and reported by PharmaBiz.com, analyzed over 300 AML patient samples and found that pairing venetoclax, a common first-line AML therapy, with palbociclib, an FDA-approved breast cancer drug, produces substantially stronger and more durable anti-leukemia activity than venetoclax alone. Among 25 drug combinations tested, this pairing proved most effective, offering renewed promise for the approximately 20,000 Americans diagnosed annually with this aggressive malignancy.
AML remains one of the most challenging cancers to treat. Since venetoclax’s FDA approval in 2019, the drug combined with azacitidine has become the standard treatment for many AML patients, significantly improving initial response rates. However, nearly all patients eventually develop resistance, limiting long-term survival—currently only 25-40% survive five years. This universal resistance problem motivated researchers to search for solutions.
The key to the breakthrough lies in understanding how AML cells develop resistance. The research team discovered that when exposed to venetoclax alone, leukemia cells adapt by increasing protein production, a survival mechanism that allows them to evade the drug’s effects. Palbociclib interrupts this adaptation by regulating the cellular machinery responsible for producing proteins, essentially shutting down a critical survival pathway. This dual-action approach prevents cancer cells from implementing their typical defense strategy.
The research team, led by Melissa Stewart, Ph.D., and her corresponding author Jeffrey Tyner, Ph.D., validated these findings using both human tissue samples and mouse models. In particularly striking results, mice implanted with human AML cells resistant to venetoclax showed no survival benefit from venetoclax alone. However, when treated with the drug combination, the majority survived 11-12 months, with one mouse surviving beyond the study’s conclusion—a remarkable outcome suggesting the combination effectively overcomes known resistance mechanisms.
Genome-wide CRISPR screening provided additional insight, revealing that the combination therapy attacks multiple survival pathways simultaneously, making it more difficult for cancer cells to develop resistance compared to venetoclax monotherapy.
Stewart brings personal passion to this work, having survived breast cancer herself and received treatment at OHSU. “The hope that research and clinical trials can bring—that’s what motivates me,” she reflects. Her experience as a cancer patient fuels her commitment to advancing treatments that could transform outcomes for AML patients.
The researchers emphasize an important principle: scientific discovery thrives when researchers remain open-minded about unexpected connections. As Tyner notes, biology can be shared across seemingly disparate cancers, making interdisciplinary approaches valuable. The team is already evaluating other breast cancer drugs similar to palbociclib to expand future clinical trial options.
While this combination has not yet been tested in humans, the researchers’ prediction based on extensive preclinical evidence is that it would mitigate most known resistance mechanisms to current standard therapy. Next steps involve moving toward clinical trials, which could revolutionize AML treatment for thousands of patients facing this life-threatening disease. This work exemplifies how persistence in following scientific data can yield unexpected therapeutic opportunities and renewed hope for patients.
