A drug form of a traditional Chinese herbal compound improved survival in brain tumor-bearing mice

Providence, Rhode Island [Brown University] — New study shows how drugs made from natural compounds used in traditional Chinese medicine work against malignant brain tumors in mice, a promising study for the treatment of glioblastoma is creating a path for

in the studyPublished in Cell Reports Medicine, researchers showed how a formulation of a compound called indirubin improved survival in mice with malignant brain tumors. They also tested new formulations that are easy to administer, bringing potential pharmaceutical approaches one step closer to clinical trials with human participants.

“What’s interesting about this drug is that it targets many key features of this disease,” said lead author and associate professor of pathology and laboratory medicine at Brown University’s Legorreta Cancer Center. Researcher Sean Lawler said: “This is attractive because this type of cancer continues to find ways to evade individual attack mechanisms.

In addition to scientists from Brown’s Legorreta Cancer Center and School of Engineering, the team included neurosurgeons from Brigham and Women’s Hospital/Harvard Medical School and researchers from Phosphorex, Inc./Cytodigm, Inc. rice field.

Glioblastoma is the most common and aggressive brain tumor. Standard treatments are chemotherapy, radiation, and surgery, which may improve symptoms but do not cure or stop the cancer.

According to researchers, indirubin is a natural product found in indigo and is a constituent of Tangkei Ryukigan, a traditional Chinese herbal medicine that has been used to treat chronic myelogenous leukemia. Derivatives of indirubin have demonstrated cancer therapeutic potential through a variety of mechanisms. A study published ten years earlier by Lawler et al. showed that indirubin slowed the growth of glioblastoma tumors in mice. But researchers couldn’t explain why, he said. Additionally, the modified drug was not easy to work with, making it difficult for scientists to test dose levels and effectively deliver it to tumors.

Phosphorex, a Massachusetts-based biomedical company, contacted me as the scientists continued to study the compound. Phosphorex develops technologies to improve pharmaceutical formulations. Phosphorex has patented a formulation of indirubin called 6′-bromoindirubin acetoxime (BiA), which facilitates the use of this compound as an injectable cancer treatment.

The researchers tested a nanoparticle formulation of BiA on glioblastoma tumors in mice, focusing on how the drug affects the immune system.

BiA not only slowed tumor cell growth and proliferation (confirming the results of previous studies), but also improved survival through its effects on key immunotherapeutic targets.

“This drug impacted the immune system in these mouse studies in ways that could enhance clinical immunotherapy in humans,” said Lawler, who is in charge of laboratory therapeutic approaches for the treatment of brain tumors. explained.

With a grant from the National Cancer Institute, the researchers will study how it interacts with chemotherapy and radiation with the aim of developing a clinical trial for glioblastoma participants. Scientists have been studying glioblastoma for decades, but so far Lawler says there have been no significant therapeutic breakthroughs. There weren’t many.

“Over the past two decades or so, there have not been many notable discoveries that have had a meaningful impact on survival, so we are very keen to find new approaches,” said Lawler. “This research offers a new approach, which is why we are so excited.”

Additional contributions from Brown included Jorge Luis Jiménez Macias, a postdoctoral researcher in Lawler’s lab. Curt Pennell Professor of Engineering. Katherine Mantz Assistant Professor of Engineering.

This work was supported by the National Cancer Institute (RO1CA166172, R50-CA243706, R21CA259734) and the National Science Foundation (1919870).