“That was the day we found out she likely wouldn’t make it to 7,” Jennifer’s mom, Libby Kranz, told me recently. Jennifer had an especially aggressive form of a deadly childhood cancer called diffuse intrinsic pontine glioma. Sadly, she died less than four months after being diagnosed.
During Jennifer’s illness, Libby and her husband, Tony Kranz, heard about the work of Stanford pediatric neurooncologist Michelle Monje, MD, PhD, who studies donated DIPG tumor tissue to understand how its biology might be targeted with new treatments. In their final appointment at Lucile Packard Children’s Hospital Stanford, the Kranzes asked if they could donate their daughter’s tumor for this research after her death.
“They said ‘Yes, here is the paperwork,’ and we signed it,” Libby said. Then she realized the donation form asked only for consent to study the tumor on Jennifer’s brainstem, making no mention of the metastases that had spread to the frontal lobe of her brain and down her spine.
“But we want to donate all of it,” Libby told Jennifer’s oncologist, Sonia Partap, MD. The Stanford team made the arrangements, and Libby also asked Monje to try to figure out how Jennifer’s tumor had spread so fast.
Today, Monje and her colleagues are publishing a scientific paper that provides an important part of the answer. Jennifer’s tumor tissue was “the key tool to figuring this all out,” Monje told me.
The new paper, appearing in Cell, asks why high-grade gliomas — cancers like DIPG and glioblastoma — often metastasize to a specific part of the brain. As Jennifer’s did, these tumors tend to spread to a brain region called the lateral ventricle subventricular zone, an area where new nerve cells can grow throughout life. The researchers’ work revealed that some of the molecular signals promoting neural growth also attract tumor cells. A protein called pleiotrophin — secreted by neural precursor cells in the subventricular zone — was especially important in this regard. Interrupting pleiotrophin signaling dramatically reduced the spread of high-grade gliomas in mice, the researchers found.
The finding has interesting similarities to another piece of Monje’s work. In 2015, her team found that a protein important for the formation of synapses promotes the growth of high-grade gliomas. Monje explained the parallel in an interview with Cell:
One of the fascinating themes emerging from our work and the work of others is the malignant subversion of mechanisms involved in neurodevelopment and ongoing neural plasticity.
In other words, she adds, cancer can hijack the brain’s growth factors.
There’s a hopeful angle to the new findings, too: Researchers have begun developing drugs that inhibit the actions of pleiotrophin. Unfortunately, these don’t yet penetrate the brain well enough to treat high-grade gliomas. But Monje’s team showed that, in principle, such drugs should make a significant dent in gliomas’ ability to grow and spread.
After Jennifer’s death, Libby Kranz started a foundation, Unravel Pediatric Cancer, to raise awareness and money for pediatric cancer research. (The foundation helps fund Monje’s work. The new research also received funding from several other organizations that support childhood cancer research, including the Childhood Brain Tumor Foundation, the McKenna Claire Foundation and the Lyla Nsouli Foundation.)
Given her personal connection to the research, how does Kranz feel about the new discovery?
“It’s wonderful and devastating,” she told me. “It’s devastating because it’s three years too late for my daughter.” But she’s glad for the impact that Monje’s research will have on other families who face DIPG.
“DIPG parents are given no hope on diagnosis,” Kranz said. “This research has the potential to give hope, and that is invaluable.”
Previously: Moving toward multi-pronged treatment for the worst childhood brain tumor, A look at scientists’ efforts to conquer a deadly brain tumor and Stanford brain tumor research featured on “Bay Area Proud”
Photo of Jennifer Kranz courtesy of the Kranz family