The last decade has seen tremendous progress towards developing effective precision treatments for pediatric low-grade gliomas (pLGG), the most common pediatric brain tumor. However, it is becoming increasingly clear that significant challenges remain as not all children respond to targeted treatments or they respond initially, then experience rebound growth when treatment stops.

The Pediatric Brain Tumor Foundation, the largest patient advocacy funder of pediatric brain tumor research, is investing nearly $400,000 in two new basic science research projects helmed by Dr. Mimi Bandopadhayay at the Dana Farber Cancer Institute (www.bandolab.org). These projects focus on understanding how interactions at the cellular level between a child’s developing brain and their brain tumor affect the tumor’s growth, as well as how and why certain inhibitor treatments change these interactions in some patients, but not others.

Funding for both grants was made possible in part by Jack’s Drive 55, a fundraising initiative benefiting PBTF in honor of a pLGG survivor named Jack.

“When Jack was in treatment and we were yearning for a success story, PBTF gave us hope. Now that Jack’s tumor is stable, we want to do whatever we can for other families,” says his father Tony. “We’re proud to partner with PBTF to redefine how pediatric low-grade gliomas and other brain tumors are treated so that one day doctors can truly stop these tumors in their tracks, eliminate the chance of them returning, and prevent children from being left with the side effects that chemotherapy and surgery can cause. Together, we got this.”

Read Jack’s story here and learn more about the two grants below:

Optimizing targeted inhibition to overcome resistance and/or rebound resistanceNumerous small molecule inhibitors have exhibited significant promise in early phase clinical trials for treating pLGGs. However, not all patients respond positively to these treatments, and the long-term use of these inhibitors and their potential effects on both normal development and the tumor’s natural history remains unknown. PBTF’s funding of $190,047 aims to help researchers understand how interactions between developing normal brains and pLGGs affect the growth trajectory of the tumors and how MAPK inhibitors affect this interaction. Researchers also aim to understand how plasticity across cell states within pLGGs influences patients’ response and rebound to targeted inhibitors. Ultimately, this knowledge will be used to determine strategies to optimize the use of MAPK inhibitors to induce apoptosis rather than dormancy of pLGG cells, while minimizing effects on brain development.

Dissecting cellular interactions in PLGGThe growth of pLGGs, which occurs in the context of a developing brain but then stalls during adulthood, is likely to depend upon interactions between cancer cells and cells within their micro-environment. Researchers’ initial efforts to identify and characterize the cells that comprise pLGGs have indicated substantial cellular heterogeneity, both among tumor cells and co-existing normal cells, with enrichment of immune cells including macrophages, T-cells and microglia. However, the cellular interactions between pLGG cells and surrounding cells and their role in regulating tumor growth have not been defined. Current single-cell RNA-sequencing efforts are performed in single-cell dissociations that do not maintain the three-dimensional architecture of gliomas. PBTF’s funding of $204,686 for this project will help researchers apply multiplexed spatial transcriptomic and proteomic profiling to evaluate cell-cell interactions within pLGGs.

About the Pediatric Brain Tumor Foundation

Every day, 13 children and teens are diagnosed with a brain tumor, the deadliest childhood cancer. Every day after, they’re in a fight for their life. It’s a fight the Pediatric Brain Tumor Foundation is here to help families win. The largest patient advocacy funder of pediatric brain tumor research and leading champion for families and survivors, PBTF’s mission of Care. Cure. Thrive. reflects our 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 work together to put kids first. Learn more at www.curethekids.org.

 

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