There is a group of extremely hard-to-treat, aggressive tumors called diffuse midline gliomas (DMGs) – including diffuse intrinsic pontine glioma (DIPG), spinal cord glioma, and thalamic glioma. They represent the dominant cause of childhood brain cancer-related deaths in America. Usually, children between 4 to 12 years old are affected, and most die within a year of diagnosis. It is rare, affecting only a few hundred children a year, but it is proving one of the toughest to defeat.
Now, a research team from the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, have discovered a pair of drugs that work in unison to kill DMG cancer cells and even counter the genetic mutations that cause DMGs. The combination was found by AI bots that had been programmed to screen 9,000 possible fusions. The study has been published in the journal Science Translational Medicine.
Dr. Michelle Monje, the Stanford neurooncologist who led the research and is a pioneer DIPG research in the US, said:
Very few cancers can be treated by a single drug. We’ve known for a long time that we would need more than one treatment option for DIPG. The challenge is prioritizing the right ones when there are thousands of potential options. We’re hopeful that this combination will help these children.
The researchers tested the unique combination of drugs on mice (and in the lab using human cells), and it improved their rate of survival by 20%. The two drugs are panobinostat and marizomib. Panobinostat alone is used to fight cancer of the plasma cells. Marizomib alone is an experimental drug designed to treat brain tumors. Together, they are more effective at killing cancer cells than each one is by itself.
Dr. Monje told The Daily Mail:
The benefit is modest. Successfully treating this seemingly intractable disease will require a combination of approaches that also includes targeting… immunotherapeutic opportunities and important microenvironmental interactions. It is our hope that this study will help to put some of the pieces of the puzzle together towards a multi-pronged strategy against this lethal cancer.
The analysis also revealed a vulnerability in the cancer cells that nobody knew about before. The scientists could potentially exploit it to develop new strategies against childhood brain cancer.
First author Grant Lin, Ph.D., at Stanford University School of Medicine, said:
The panobinostat-marizomib drug combination exposed an unknown metabolic vulnerability in DIPG cells. We didn’t expect to find this, and it represents an exciting new avenue to explore in the development of future treatment strategies for diffuse midline gliomas.
Monje concludes that the panobinostat-marizomib combo could be an essential component in a multitherapy strategy. Such a plan would also include approaches that disrupt factors in the tumor microenvironment, which the glioma cells depend on to grow and harnessing the immune system.
