Anti-malarial drug pyronaridine could be repurposed to treat cancer

Can a drug that's used to treat malaria be repurposed to fight cancer? Researchers at The University of Texas at El Paso have secured a patent for the anti-malarial drug pyronaridine to do just that. Pyronaridine has been used to treat the mosquito-borne infectious disease for over 30 years.

The discovery is the result of a serendipitous encounter at UTEP.

Renato Aguilera, Ph.D., a UTEP professor of biological sciences, attended a University seminar about the drug in 2017. As a longtime cancer researcher, Aguilera realized that the molecular structure of pyronaridine could be useful in fighting cancer cells.

Louis Pasteur said 'Chance favors the prepared mind.' When I looked closely at the structure of the drug, I saw that it could be used to attack cancer cells. Several year later, the granting of the patent is getting us closer to actually using this drug for patient care."

Renato Aguilera, Ph.D., UTEP professor of biological sciences

Along with then doctoral student Paulina Villanueva, Ph.D., Aguilera conducted extensive lab research to identify how pyronaridine interacts with cancer cells. In 2018, they published a research paper in the journal PLOS One outlining their findings that, in test tubes, the drug slows the replication of cancer and induces "cellular suicide" in leukemia, lymphoma, melanoma, multiple myeloma, lung, ovarian and breast cancer cells.

Cancer cells multiply much faster than normal cells in the body, Aguilera explained, which leads to the cancer spreading and a worsening prognosis for the patient.

In their research, Aguilera and Villanueva found that pyronaridine interfered with the activity of an enzyme called topoisomerase II, which helps cancer cells replicate, thus slowing the progression of the cancer growth. Along with slowing them down, it also spurred the cancer cells into "programmed cell death," a process by which cells effectively commit suicide. 

Moreover, the drug did not affect normal cells that were not rapidly dividing, leaving healthy cells intact while killing the cancer cells, Aguilera said.

"With pyronaridine, we have the trifecta: slowed growth of cells, programmed cell death, and minimal impact to healthy cells," Aguilera said. "In the future, this drug could potentially be used in combination with immunotherapy to speed up the process of killing cancer cells."

Pyronaridine has been successfully tested in some animals, Aguilera said, and a pilot study on terminally ill patients with late-stage breast, lung and liver cancers by pharmaceutical firm Armaceutica showed increased longevity. But Aguilera cautioned that before pyronaridine can be used to treat cancer in the general public, it must undergo clinical trials, a yearslong process that tests drugs to ensure their safety and efficacy in humans.

Villanueva is now a postdoctoral research scholar at the NanoScience Technology Center at the University of Central Florida. During her doctoral program at UTEP, Villanueva conducted much of the research that led to the discovery of pyronaridine as an anti-cancer drug.

"It's incredible to witness the hard work invested in this research come to fruition," Villanueva said. "Research opens the door to countless possibilities, and although personalized medicine isn't one-size-fits-all, the drug pyronaridine could be a breakthrough for some. The journey isn't over yet - there's still much to be done - but securing the drug's patent is a significant milestone that will drive future progress."

The drug was patented this spring in partnership with Armaceutica, which works to develop treatments for cancer. The patent, which is granted by the United States Patent and Trademark Office, recognizes Aguilera as the inventor and intellectual property owner when it comes to the use of pyronaridine for cancer.