What is Diffuse Intrinsic Pontine Glioma (DIPG)?

Meagan Bebenek passed from a Diffuse Intrinsic Pontine Glioma tumour over 25 years ago. Her story and the determination of her mother Denise that no family should have to face that path alone brought Meagan Bebenek Foundation into being and continue to inspire its staff, volunteers, and donors today.

What is Diffuse Intrinsic Pontine Glioma?

Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brain cancer that occurs in the brainstem, the part of the brain that connects to the spinal cord. It is diagnosed in 20-30 Canadian children each year, most commonly in those 5-10 years of age [1, 2]. Unfortunately, DIPG is currently incurable, with a median survival time of less than one year [1].

DIPG is named for some of its key characteristics. “Diffuse” refers to the tumour’s lack of defined borders. Instead of a distinct barrier between the cancer and normal tissue, cancer cells are mixed in with normal brainstem cells. “Intrinsic pontine” refers to the tumour’s location. DIPG arises within the pons, a part of the brainstem that controls important vital functions like breathing and heart rate. “Glioma” is a type of brain cancer that arises from glia, brain cells that are not neurons, but play important roles in nutrient production, immunity, structural integrity, and even brain signaling. 

What causes DIPG? 

There are still a lot of unknowns regarding how DIPG arises. It is not associated with any environmental or demographic risk factors. From analyzing patients’ tumour samples, scientists have discovered DNA mutations that most DIPG tumours have in common [3, 4], and they have shown that DIPG arises during prenatal or early childhood development when cells are dividing frequently to grow the brain [5]. Some glia undergo genetic changes that cause them to get stuck in growth mode, leading to DIPG formation [5, 6].

How is DIPG diagnosed and treated?

Usually, DIPG is diagnosed with brain imaging. In some cases, a doctor may take a sample of the tumour by performing a surgical procedure in which a specialized needle is inserted through a small hole in the skull [7]. Analysis of this tumour sample can aid diagnosis and sometimes reveal eligibility for clinical trials [1].

Treating DIPG involves radiation therapy, which can improve symptoms and prolong life but does not improve overall survival rates [2]. DIPG tumours cannot be removed surgically because of their location in crucial brain regions regulating breathing and heart rate. Combined with the tumour’s lack of defined borders, this makes it impossible to remove without disturbing vital functions. 

The blood-brain barrier, a natural defense mechanism in which the walls of the brain’s blood vessels are especially fortified to protect the brain, remains intact in DIPG, which means that drugs administered into the bloodstream have difficulty accessing the tumour. This may be part of the reason that chemotherapy has limited effectiveness against DIPG [2, 6].

Due to these challenges, and the aggressiveness of DIPG tumours, less than 1% of children with DIPG will survive more than 5 years after diagnosis, and there is an urgent need for new treatment strategies [6].

Hope through research

Meagan Bebenek Foundation supports projects at the SickKids Brain Tumour Research Centre (BTRC) aiming to improve knowledge and treatment of DIPG. Labs at the BTRC have been instrumental in some of the most impactful DIPG research and continue to work at the cutting edge of discovery.

Investigating DIPG formation and early detection

The Hawkins lab at the BTRC was at the forefront of the discovery of the most common tumour-driving mutations in DIPG over 10 years ago [3]. Today, with the support of MBF, they are investigating genetic changes that cooperate with those driving mutations at the origin of a DIPG tumour (2025 MBF seed grant: Deciphering the genetic changes that lead to DIPG formation).

An MBF-funded project in the Dirks lab at the BTRC is also investigating the origins of DIPG tumours, focusing on what types of cells in the developing brain are the most vulnerable to DIPG-causing mutations (2024 MBF seed grant: Discovering how diffuse midline glioma begins). These kinds of projects increase our understanding of how DIPGs form in their earliest stages, potentially informing early detection of tumours in the future.

Investigating new treatment strategies 

Targeted therapy is a promising area of research that involves discovering treatments that target a unique aspect of a cancer while leaving normal cells unharmed. The Hawkins lab is targeting DIPG by depriving it of specific combinations of nutrients, without affecting healthy cells (2024 MBF seed grant: Metabolic vulnerabilities of Diffuse Midline Glioma). Their results show that this strategy could increase DIPG’s susceptibility to radiation treatment. That would mean lower radiation doses for patients, reducing harmful side effects.

MBF funding supported the Rutka lab at the BTRC in pioneering a new method of delivering anti-cancer drugs to DIPG tumours. Findings from initial tests in mice showed that using ultrasound waves to disrupt the blood-brain barrier near the tumour allowed more drug to reach the cancer [8]. The results were promising enough that they launched the first ever clinical trial of this method in pediatric patients [9]. They are excited to report positive early results showing the treatment is feasible and safe.

Taking care of tissue donations for current and future research 

Tumour sampling for diagnosis is not as common for DIPG as for other cancer types, making donated samples a precious resource [2, 7]. The BTRC is in a privileged position to access samples from participating DIPG patients diagnosed and treated at SickKids. Samples are received, processed, catalogued, and stored by the NEUROcore Biobank, a collection of biological samples from over 1800 brain tumour patients. It is an invaluable resource to the researchers at the BTRC. MBF funding has supported the Biobank for many years and most recently has allowed them to hire new staff, expand to include more tissue types, and improve collection and storage techniques to keep up with cutting-edge research methods (2025 MBF seed grant: NEUROcore Biobank).

When Meagan Bebenek was diagnosed with DIPG, we knew a lot less about the mechanisms behind the disease. Thanks to DIPG researchers, we now understand the most common mutations that drive DIPG formation, we are discovering new ways to target the disease’s vulnerabilities, and we are developing new methods of administering treatment. These new avenues of research each represent a chance to improve survival and quality of life for children diagnosed with DIPG.

1. Fonseca, A., et al., Pontine gliomas a 10-year population-based study: a report from The Canadian Paediatric Brain Tumour Consortium (CPBTC). J Neurooncol, 2020. 149(1): p. 45-54.

2. Warren, K.E., Diffuse intrinsic pontine glioma: poised for progress. Front Oncol, 2012. 2: p. 205.

3. Khuong-Quang, D.A., et al., K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol, 2012. 124(3): p. 439-47.

4. Wu, G., et al., Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet, 2012. 44(3): p. 251-3. 

5. Liu, I., et al., The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nature Genetics, 2022. 54(12): p. 1881-1894. 

6. Weisbrod, L.J., et al., Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies. Cancer Letters, 2024. 590: p. 216876. 

7. Chaturvedi, A., et al., Safety and Efficacy of Biopsy in Patients with Diffuse Intrinsic Pontine Gliomas. World Neurosurg, 2024. 187: p. e870-e882. 

8. Ishida, J., et al., MRI-guided focused ultrasound enhances drug delivery in experimental diffuse intrinsic pontine glioma. J Control Release, 2021. 330: p. 1034-1045. 

9. World first: Sunnybrook and SickKids clinical trial delivers chemotherapy to pediatric brain tumours using MRI-guided focused ultrasound. 2023; Available from: https://www.sickkids.ca/en/news/archive/2023/world-first-sunnybrook-sickkids-clinical-trial-chemotherapy-pediatric-brain-tumours-mri-guided-focused-ultrasound/.