Collaborative Corner

Racing To Find Cures for DIPG Brain Tumors in Children

Diffuse Intrinsic Pontine Glioma (DIPG) is a rare form of pediatric brain tumor located in the pons (middle) of the brain stem. “Glioma” is a general term used to describe any tumor that develops within glial tissue, a type of supportive tissue that keeps neurons in place and functioning.  

According to the Dana-Farber/Boston Children’s Hospital Cancer and Blood Disorders Center, 10% of all childhood brain/CNS tumors are DIPGs. Approximately 300 children in the U.S. each year are diagnosed with these tumors.  

What makes DIPGs so detrimental to children is their rate of growth, as well at their location in the brain. The brainstem is responsible for a number of bodily functions essential for human life including sleeping, breathing, heart rate regulation, and eating.  It also controls motor and sensory systems in the body; affecting sight, hearing, touch, and movement.

Sadly, DIPG brain tumors have a 5-year survival rate of less than 1%, and, on average, become fatal approximately 9 months post-diagnosis.

Because these tumor cells are diffusely infiltrating – that is, growing amidst healthy nerve cells as opposed to a singular mass of tumor cells – and located in a highly sensitive area of a child’s brain, they generally cannot be surgically removed.  Surgical procedures in this area of the brain can cause severe damage to neural systems responsible for arm, leg, and eye movement, as well as breathing, swallowing, and even consciousness.

The current standard of care for DIPG is radiation therapy, which uses high-energy x-rays to kill cancer cells and shrink tumors. Typically administered over the course of 6 weeks, this form of treatment can help temporarily with symptom relief and result in transient shrinkage of tumor size; however, radiation can not cure DIPG.

Currently, chemotherapy has not shown improvement in survival for children with DIPG.  However, there are numerous clinical trials underway to advance the effectiveness of chemotherapy and other drugs.  This includes the development of new drugs that could increase the effectiveness of radiation therapy (called radiosensitizers), the exploration of immunotherapy treatments, and the development of drugs that could alter the structure of the tumor cells or the environment that allows them to propagate.

It is unknown what exactly causes a child to develop a DIPG brain tumor, however recent research has suggested that DIPG tumor formation may be linked to brain development, which is supported by the fact that most patients with DIPG are diagnosed between the ages of 5 and 10 years old. Another possible cause of these tumors could be genetic and epigenetic mutations within the cells of the brain stem.  But more research is needed to determine what exactly causes these mutations to occur.

 

Research is Underway

The CBTTC has partnered with a number of research initiatives including the Pacific Pediatric Neuro-Oncology Consortium (PNOC) to collect DIPG data and biosamples toward assisting researchers and clinicians around the world in developing new clinical trials and treatment strategies to address DIPG brain tumors in children.  

Queryable on a number of platforms including PedcBioPortal, CAVATICA, and the Gabriella Miller Kids First Data Resource Portal (as part of the CBTTC’s Pediatric Brain Tumor Atlas dataset), the CBTTC is harmonizing and annotating a regularly growing collection of DIPG whole genome sequenced, phospho proteomic, treatment, and outcome data with matched available biospecimens. 13 DIPG cell lines have been generated for pre-clinical lab research, and more than 20 CBTTC biospecimen and data projects studying DIPG are currently in progress.  

Recently-developed immunotherapies have led to incredible breakthroughs in the treatment of pediatric leukemias over the past five years. A number of researchers across the CBTTC’s network of collaborating partners are working to translate these currently-available immunotherapy methods for leukemias into therapies for pediatric brain tumors including DIPG.  CBTTC investigator, Dr. Michelle Monje of Stanford University, for example, has recently demonstrated that a form of CAR T Cell Immunotherapy can kill DIPG cells in mice. She and her research team are currently planning a human clinical trial for this treatment.

 

CBTTC Biospecimen and Data Projects to study DIPG Brain Tumors include:

CBTTC Data Project 01: Hideho Okada on DIPG and Other Primary Pediatric Brain Tumors

CBTTC Biospecimen Project 03 (a,b,c): Genomic Evaluation of Malignant Pediatric Cortical Tumors

CBTTC Data Project 04: Immunotherapeutically-Targeting IDO1 in Pediatric High-grade Glioma

CBTTC Biospecimen Project 11: Targeting Replicative Stress in Pediatric Brain Tumors with ALT

CBTTC Data Project 17: Integrated Genomic Analysis to Elucidate the Role of the PIK3CA and 10q LOH as Unique Drivers and Cooperating Events in Pediatric High-grade Gliomas

CBTTC Biospecimen Project 27: Cracking the Histone Code: Characterizing Pediatric Brain Tumor Epigenetics Using Cerebrospinal Fluid

CBTTC Biospecimen Project 28: GPC2 As an Immunotherapeutic Target in Medulloblastoma and Other Pediatric Brain Tumors

CBTTC Data Project 37: Comprehensive Genomic and Immune Signature Profiling of Ependymoma and Diffuse Intrinsic Pontine Glioma

Researchers and clinicians anywhere can submit requests for access to CBTTC data and biospecimens for more than 30 pediatric brain tumor types including DIPG.  To learn more, visit https://cbttc.org/research/specimendata/.

To see our full list of CBTTC scientific biospecimen projects, visit  https://cbttc.org/research/scientific-projects-biospecimen/.
To see our list of scientific data projects, visit https://cbttc.org/scientific-projects-data/.

 

New Partnerships to Accelerate Research

Project Open DIPG is an exciting recent partnership between the CBTTC and PNOC, led by Drs. Adam Resnick, PhD of Children’s Hospital of Philadelphia and Javad Nazarian, PhD, MSC of Children’s National Health System. This global collaboration seeks to empower discovery of improved treatments for children diagnosed with DIPG through a system of data-driven clinical trials and innovative research techniques.

The project is also leveraging the strength of these two consortia’ combined-global network of 37 member institutions to race toward discoveries, innovations, and effective treatment strategies for this difficult-to-treat form of cancer.

Using a “team science” approach, Project Open DIPG is building upon PNOC’s expanding clinical portfolio and CBTTC’s expertise in collecting and analyzing biospecimen-driven research data. The project is collating and releasing newly-generated, DIPG-omic and clinical data, including liquid profiling of cerebrospinal fluid (CSF) and plasma, DNA methylation, copy-number variation (CNV), proteomics, whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA-seq from individual investigator labs and consortia efforts on a rapid, pre-embargo release cycle. To date, 460 clinical research subjects have been enrolled with corresponding biospecimens collected and 5070 files of data generated.

 

Support for DIPG Research

Philanthropic support has been critical in the development of DIPG clinical trials, data analysis, and programmatic growth across the U.S. and beyond.  A number of foundations, including the Pediatric Brain Tumor Foundation, the Kortney Rose Foundation, Dragon Master Foundation, Grey Matters, The Lilabean Foundation, Smashing Walnuts, Kisses 4 Kayla, Swifty Foundation, Rally Foundation, The Brad Kaminsky Foundation, The Childhood Brain Tumor Foundation, The Matthew Larson Foundation, and the Musella Foundation have been key drivers in the development of the Open DIPG project, providing pivotal financial support to the development of clinical trials, new therapeutic strategies, biospecimen collection and analysis, and research administration.

 

Giving the Gift of Life

Understanding the biological underpinnings of a brain tumor is a complex and delicate process. Researchers need samples of brain tumor tissue to better understand how brain tumors form and how they can be treated. As more tissue samples are collected, researchers are able to match more effective treatments to each patient.  

The CBTTC is consistently inspired and humbled by so many families, who in the face of receiving the devastating news that their child has been diagnosed with a DIPG or other form of childhood brain cancer, resolve to take action for the benefit of children everywhere by consenting to donate brain tissue toward research efforts across the CBTTC network of research institutions.

Spearheaded by CBTTC supporters, the Swifty Foundation, and supported by an additional 13 pediatric brain cancer foundations, the Gift from a Child initiative was launched to increase pediatric brain tissue donations through advocacy as well as the education of families enduring the worst … the loss of a child.  The program has formed partnerships with the best researchers and medical providers who value information and data sharing. These strategic partnerships will accelerate breakthroughs in cancer research, improve treatments and ultimately curing childhood brain cancer.

To learn more about the Gift From a Child program, visit https://giftfromachild.org/

 

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