Targeting DIPG With Collaboration and Innovation

Maryam Fouladi, MD

Maryam Fouladi, MD, MSc, FRCP, is a pediatric neuro-oncologist, co-executive director of the pediatric neuro-oncology program at Nationwide Children’s Hospital.

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Diffuse intrinsic pontine glioma (DIPG) is rare, with only 200-300 cases diagnosed in children each year in the United States. Its location in the brain’s pons makes it hard to access for biopsy or drug delivery. The diffuse nature of the tumor also makes it essentially unresectable; tumor cells cannot be removed without taking vital healthy tissue with them. 

Maryam Fouladi, MD, pediatric neuro-oncologist and the new co-executive director of the Pediatric Neuro-Oncology Program at Nationwide Children’s, founded the CONNECT Consortium in 2012 to help build a network of patients and clinicians focused on the rare and deadly tumor. The international collaborative of pediatric cancer research and clinical care centers exists to improve outcomes for children with high-risk brain tumors such as DIPG and other high-grade gliomas and is now based out of Nationwide Children’s. 

 

“DIPG is a wily tumor,” says Dr. Fouladi, who is currently leading a trial to test efficacy and safety of combining a BMI-1 inhibitor with radiation therapy in children with DIPG and other high-grade gliomas (CONNECT1702); the study is based on findings from basic science collaborations with Rachid Drissi, PhD, principal investigator in the Center for Childhood Cancer and Blood Diseases at Nationwide Children’s, and others, described in a 2020 publication in Molecular Cancer Research. “It develops resistance and survives through multiple different pathways, so we will need a multi-pronged approach to trying to cure it.” 

“We want to build on what we know works right now — radiation — not just throw every method at these children and adversely affect their quality of life,” says Dr. Fouladi. “We want to judiciously, carefully conduct clinical trials looking at both toxicity and efficacy, combining radiation with chemotherapy, immunotherapy or targeted therapy. Progress will be incremental, but in the end, all of these are likely to become part of an effective armamentarium against DIPG in some way.” 

The DIPG Registry — also founded and chaired by Dr. Fouladi to advance DIPG research via the collection and sharing of tissue samples — includes more than 1200 patients at about 115 sites in 15 countries, pooling clinical imaging, pathology findings and tissue samples to enable large-scale studies of DIPG biology. The registry has enabled 140 disease models and more than 30 collaborative studies, with numerous publications to share valuable data with the broader scientific community. The registry’s genomics efforts will now be based out of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital. 

REFERENCES:
Senthil Kumar S, Sengupta S, Zhu X, Mishra DK, Phoenix T, Dyer L, Fuller C, Stevenson CB, DeWire M, Fouladi M, Drissi R. Diffuse intrinsic pontine glioma cells are vulnerable to mitotic abnormalities associated with BMI-1 modulation. Molecular Cancer Research. 2020 Nov;18(11):1711-1723.