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Research Investment from the PLGA Fund at PBTF Results in Publication that Provides Clinicians Guidance When Treating a Sub-Group of PLGG Patients

07/13/21

The Pediatric Brain Tumor Foundation’s PLGA Fund helped support research that led to valuable insight and a shift in strategy towards a molecularly targeted approach for treating a subset of the most common type of brain tumor in children, pediatric low-grade gliomas (PLGGs). The research findings, under the direction of Drs. Maryam Fouladi and Lindsey Hoffman at Cincinnati's Children's Hospital, and published results are critically important in guiding targeted therapeutics and diagnostic biopsy at recurrence.

In Characterizing Temporal Genomic Heterogeneity in Pediatric Low-Grade Gliomas, published in Acta Neuropathologica Communications, researchers from five different medical institutions explored the genetic aberrations within the mitogen-activated protein kinase (MAPK) pathway.

While the treatment for PLGG patients increasingly incorporates genomically-driven therapy, challenges continue to plague many patients with incomplete resections and/or progressive disease. Moreover, those patients may experience a chronic relapsing course, given relatively low durable response rates with standard chemotherapy and unacceptable long-term toxicity of irradiation. Thus, an adequate understanding of the evolution of PLGG genomic profiles is vital in guiding diagnostic and treatment decisions at recurrence. 

This research aimed to inform about genomic profiles for patients grouped by histologic diagnosis. The report characterizes temporal genomic heterogeneity in the PLGG cohort and offers novel findings with important therapeutic implications.

The investigators demonstrated that most actionable genetic alterations in PLGG, including BRAF fusions or mutations, are conserved at recurrence after prior systemic therapy or irradiation treatment. While repeat biopsy is likely, it is not necessary to confirm preservation of BRAF alteration status. Histologic diagnosis and grade remained the same in all tumors with no acquisition of H3K27M mutations or evidence of malignant transformation. However, over time, changes in the CKDN2A deletion status were demonstrated, and acquisition of homozygous CDKN2A deletion may define a higher risk sub-group of PLGG with a poorer prognosis.

Given the potential for targeted therapies for tumors harboring CDKM2A deletions, performing a biopsy at recurrence may be indicated in certain patients, especially those with rapid progression. These findings may influence clinical treatment and follow-up for a sub-group of PLGG patients.

PBTF is proud that the research we fund has paved the way for more focused efforts to understand childhood brain tumors' cellular and molecular biology. In addition, this investment has opened avenues for the discovery of new diagnostic and treatment approaches. We are grateful to our donors and supporters for helping PBTF foster innovation in the field and making us the world's leading nonprofit dedicated to a world without childhood brain tumors. Learn more about the research we fund at www.curethekids.org/research.

About the Pediatric Brain Tumor Foundation
Every day, 13 children and teens are diagnosed with a brain tumor, the deadliest and most common form of cancer in kids under 15. Every day after, they are in a fight for their life. It's a fight the Pediatric Brain Tumor Foundation is here to help families win. A leader in the brain tumor and childhood cancer communities, PBTF's mission of Care. Cure. Thrive. reflects its commitment to curing all pediatric brain tumors and transforming how children and their families are cared for. Since 1991, PBTF has provided strategic leadership and funding to accelerate the number of targeted therapies for children battling brain tumors today, while equipping families with the patient family education, financial relief, and emotional support they need to navigate their child's journey. A world without childhood brain tumors is possible when we stand together to effect real, meaningful change. Learn more at www.curethekids.org.