A New Pathway for Treating Deadly Children’s Brain Cancer

A team of international researchers have discovered a new pathway for treating Diffuse Intrinsic Pontine Gliomas (DIPG), an incurable form of children’s brain cancer. Their results were published in Nature Communications.

DIPG is a highly aggressive and inoperable tumor that grows in the brain stem. It usually affects children under the age of 10, with most patients dying within a year of diagnosis. Although previous studies identified a genetic mutation called PPM1D — which is critical for cell growth and cell stress response –as a contributor to DIPG, efforts to thwart the PPM1D mutation have proven ineffective at controlling DIPG.

The research team, comprised of researchers from Yale University, University of Iowa, and the Translational Genomics Research Institute (TGen), an Affiliate of City of Hope, uncovered a vulnerability in the metabolic process for creating NAD, which a substace needed to produce cell life.

“This is really an amazing new way to attack this cancer. We found that the mutated gene PPM1D essentially sets the stage for its own demise,” said Michael Berens, Ph.D., a TGen Deputy Director, head of TGen’s DIPG research, and one of the study’s senior authors in a press release.

Moreover, the researchers found that PPM1D muzzles a gene called NAPRT, which is key to the production of the NAD substance. By silencing NAPRT unavailable, the cell then switches to another protein needed to create NAD called NAMPT. Thereby using a drug that inhibits the production of NAMPT, researchers were able starve to death those cancer cells with the PPM1D mutation.

Findings Offer ‘New Hope’

“It is such a devastating disease, and we have been so stymied in our progress for new DIPG therapies. Many drugs have been tested with no success at all. These findings now offer new hope for children with this truly terrible disease,” said another senior author Ranjit Bindra, M.D., Ph.D., Associate Professor of Therapeutic Radiology at the Yale Cancer Center, where he treats children with DIPG.

Charles Brenner, Ph.D., Chairman of Biochemistry at the University of Iowa, and one of the study’s lead authors said: “Our study’s potential translational impact should lead to clinical trials and renewed hope for these families who face such a difficult diagnosis for their child.”