Existing drug shows early promise against deadly childhood brain tumor

An existing drug may help treat the deadliest form of childhood brain cancer, according to a Stanford-led study published this week in Nature Medicine. The findings are the first to show an effect of any FDA-approved drug on the cancer, which is called diffuse intrinsic pontine glioma (DIPG).

The drug, a blood-cancer medication called panobinostat, reduced tumor cell growth in a lab dish and lengthened survival time for mice with the tumor. Stanford’s Michelle Monje, MD, PhD, who led the research, cautioned that panobinostat has not yet been shown to work in children with DIPG. Her team is planning for a closely monitored clinical trial that will track the drug’s effects in DIPG patients.

From our press release about the new study:

The drug repairs a portion of the cellular machinery now known to be defective in DIPG tumor cells, the new research showed. “A key thing that is wrong with DIPG cancer cells gets corrected by panobinostat,” said Monje, who also treats DIPG patients in her role as a pediatric neuro-oncologist at Lucile Packard Children’s Hospital Stanford. However, the new data also showed that some DIPG cells develop resistance to the drug, which means it will likely need to be combined with other drugs to achieve the best results in humans. “I don’t think this is a cure, but I do think it will help,” she said.

The new panobinostat findings are one piece of a larger story about Monje’s efforts to understand DIPG. As we recently reported on Scope, her team has also found that nerve activity — in her study, the nerve firing needed to initiate walking — drives the growth of high-grade gliomas, including DIPG. In that work, the scientists uncovered a piece of the tumor’s molecular workings, called neuroligin-3, that could serve as a target for new drugs.

Neuroligin-3 is distinct from the cellular machinery affected by panobinostat. Ultimately, that’s a good thing, since doctors want to be able to attack the tumor in several ways, with more than one drug. (As an analogy, think of stopping a runaway train: It’ll be easier if you can apply the brakes and cut off the fuel supply.)

In addition to running clinical trials and continuing to study the basic molecular machinery of the tumor, the team plans to use DIPG cells in the lab to screen other drugs in combination with panobinostat. They are also collaborating with many other teams from around the world to try to make a difference in the outcome of this brain tumor, which currently has a five-year survival rate of only about one percent. The federal government’s clinical trials website lists all the trials underway on this tumor, for those who are interested.

“The goal is multimodal treatment to improve outcomes for children with DIPG,” Monje said.

Via Scope
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