For more than 15 years, pediatric neuro-oncologist Mariella Filbin, MD, PhD, has been on a scientific crusade to understand DIPG (diffuse intrinsic pontine glioma). She hopes to one day be able to cure a disease that has historically been thought of as an incurable type of childhood brain cancer.
“While I was in medical school, I met a young girl who was diagnosed with DIPG,” Filbin recalls. “When I heard that there was no treatment available, I couldn’t believe that was the case. It really made a huge impression on me and since then, I’ve dedicated all my research to fighting DIPG.”
Her mission brought her to Boston Children’s Hospital for her medical residency program and later, to do postdoctoral research at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Now, she’s starting her own research laboratory focused on DIPG — which has also been called diffuse midline glioma (DMG) in recent years — and continuing to treat children with brain tumors at the Dana-Farber/Boston Children’s pediatric brain tumor treatment center. She’s also a scientist affiliated with the Broad Institute Cancer Program.
This year, Filbin has made new impact in the field by leveraging the newest single-cell genetic sequencing technologies to analyze exactly how DIPG develops in the first place. Her latest research, published in Science, entailed profiling more than 3,300 individual brain cells from biopsies of six different patients.
Using what’s known as a single-cell RNA sequencing approach to interrogate the makeup of DIPG/DMG tumors, Filbin was able to identify a particularly problematic type of brain cell that acts forever young, constantly dividing over and over again in a manner similar to stem cells. …
Their plan is to optimize the ability for CAR T-cell therapies, which use a patient’s genetically modified T cells to combat cancer, to more specifically kill tumor cells without setting off an immune response “storm” known as cytokine release syndrome. The key ingredient is a unique small molecule that greatly enhances the specificity of the tumor targeting component of the therapy. …
“It’s a brutal disease; there’s just no other way to describe DIPG,” says Steve Czech. “And what’s crazy is that there aren’t many treatment options because it’s such a rare, orphan disease.”
Czech’s son, Mikey, was diagnosed with a diffuse intrinsic pontine glioma (DIPG) on Jan. 6, 2008. It was Mikey’s 11th birthday. The fast growing and difficult-to-treat brainstem tumors are diagnosed in approximately 300 children in the U.S. each year.
Sadly, the virtually incurable disease comes with a poor prognosis for most children. The location of DIPG tumors in the brainstem — which controls many of the body’s involuntary functions, such as breathing — has posed a huge challenge to successful treatment thus far.
“Typically, they give kids about nine months,” says Czech. “Our lives changed forever the day that Mikey was diagnosed.” …
DIPG isn’t like most brain tumors. Rather than forming a solid mass, it weaves itself among the nerve fibers of the pons—a structure in the brain stem that controls vital functions like breathing, blood pressure and heart rate—making it impossible to biopsy. At least, that’s been the dogma.
Brain tumors can be very difficult to treat, but at least we know what to do about them. For years, a mix of surgery, radiation and chemotherapy has been used to treat brain tumors like medulloblastoma.
These treatments are fairly successful, but for a rare, almost always fatal tumor called diffuse intrinsic pontine glioma (DIPG), we haven’t had any success—in fact, we haven’t known where to start.
The problem has to do with where DIPGs are located: nestled among the nerves in a portion of the brain stem, the pons, that controls critical functions like our breathing, blood pressure and heart rate.
“For 40 years, we lacked the neurosurgical techniques to biopsy DIPGs safely,” say Mark Kieran, MD, PhD, director of the Brain Tumor Program at Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC). “In fact, one of the first lessons every oncologist is taught still is, ‘Don’t biopsy brain stem gliomas.’ The dogma was that the risk of severe or fatal damage was too great.” And because we couldn’t biopsy them, we couldn’t study them to learn what makes them tick.”
A lot can change in four decades. Techniques for operating on the brain have advanced considerably, as have the tools for probing tumors at the molecular level. So, looking to turn the dogma about DIPGs on its head, Kieran has launched a clinical trial that aims to use advanced surgical and diagnostic tools to target and individualize DIPG treatment. …