DURHAM, N.C. (WNCN) — A drug approved to treat leukemia may have the potential to disrupt a type of breast cancer, according to a new study.
In animal studies led by researchers at Duke Cancer Institute, the drug, called asciminib, disrupted the ability of HER2-positive breast cancer tumors from colonizing in the brain.
Researchers said the studies in mice suggest the therapy could be effective for humans as well.
They hope it will help patients who are resistant to treatment and create a new approach to fighting lethal diseases.
“When tumors escape the therapies, they often metastasize in the brain,” author Ann Marie Pendergast Ph.D. said, a professor and vice chair of the Department of Pharmacology and Cancer Biology at Duke University School of Medicine. “Brain metastasis is probably the most devastating consequence of breast cancer or any other solid tumor, in that it actually diminishes the quality of life.”
Dr. Pendergast continued, “Many times the patients undergo seizures, cognitive impairment, sometimes not even able to communicate or move because of the metastasis in their brains.”
When this happens, she said treatments could be unsuccessful and it could lead to a devastating diagnosis.
This is because the tumors have developed resistance, or the therapies cannot get past the blood-brain barrier.
“What happens is when cells go to the brain, they become very difficult to treat because a lot of these drugs that are effective in the breast or other parts of the body cannot cross the blood-brain barrier very effectively,” Dr. Pendergast said.
In the study, Dr. Pendergast and her colleagues looked at how the HER2 protein promotes breast cancer growth, particularly after becoming resistant to treatments that have been proven otherwise successful at prolonging lives.
HER2 is a driving force in 30 percent of breast cancers, with about 45 percent leading to brain metastases, according to the study.
Researchers found that a pair of enzymes, ABL1 and ABL2 kinases, regulate the expression of HER2.
They said the enzymes help create the conditions that allow HER2 to accumulate on the surface of breast cancer cells. In turn, this would fuel breast cancer tumor metastasis.
In the mice, researchers said they were able to disrupt the ABL kinases with asciminib.
Unlike other approaches, asciminib is not impeded by the blood-brain barrier in tumor-bearing mice and interferes with the ABL kinases’ signaling mechanism, the study said.
By doing this, the therapy keeps the HER2 protein from manifesting in the breast cancer cells, the study finds.
It said the therapy shuts down the cells’ ability to spread.
As for next steps, the research team said it hopes to provide evidence for human trials.
If all goes well, Dr. Pendergast said human trials could take 7-10 years.
She said one of her senior graduate students, Courtney M. McKernan, was the driving force behind the study when the process began five years ago.
“I like the graduate students in my laboratory to take ownership of their project and she certainly did,” Dr. Pendergast said. “It’s very rewarding. One of the best parts of being a professor or leading independent research is to see how a student comes in the lab, sometimes knowing just barely the certain areas that we study, and then becomes an expert at it.”
Other authors include Aaditya Khatri, Molly Hannigan, Jessica Child, Qiang Chen, Benjamin Mayro, David Snyder, and Christopher V. Nicchitta.
The study received funding support from the Department of Defense, the National Institutes of Health, the National Cancer Institute and the Duke Cancer Institute and Translating Duke Health Initiative.