The seemingly insurmountable challenge presented by childhood brain tumors, particularly high-grade gliomas (HGG), has long presented a formidable challenge. However, leading-edge research from scientists at the Children’s Brain Tumor Network (CBTN) is introducing new hope by revolutionizing our understanding of these diseases. This hope is built upon the robust data available only through the Gabriella Kids First Data Resource Center (Kids First DRC) Portal.
Looking at Tumors in a New Way
Dr. Ammar Naqvi, a lead bioinformatics scientist at CBTN, is exploring “splicing variants” in the treatment of high-grade gliomas. Imagine our genes as instruction manuals that instruct our bodies on how to function. Typically, scientists study the full set of instructions all at once. But Dr. Naqvi’s team is taking a closer look at how different pieces of those instructions can be rearranged—through a process called splicing—to create slightly different versions of the same gene. By studying these slight variations, they’re uncovering details that were missed before, including new clues for potential treatments.
“Instead of looking at a gene’s activity as one overall signal, we zoomed in to examine the smaller pieces that make up the gene—called exons. This detailed view helped us find unique versions of the gene that are only found in tumors, which could lead to the identification of tumor-specific protein isoforms and new treatment targets,” said Dr. Naqvi.
A Breakthrough Discovery
This deeper look paid off. The team discovered a special version of a gene called NrCAM that appears to be present at high levels in high-grade brain tumors, whereas it is absent in healthy cells. This version of NrCAM helps tumors grow and spread—but also presents a perfect target for immunotherapy, a treatment approach that allows the immune system to attack cancer without harming healthy cells.
“What makes this target so exciting? It meets all the key criteria: it’s found in large enough amounts to be treated, it’s located on the tumor’s cell surface so that it can be reached, and—most importantly—it’s unique to the cancer tumor, which helps protect healthy tissue.”
Ammar Naqvi, PhD
Principal Bioinformatics Scientist
The discovery was made possible in large part due to the robust data available through CBTN. CBTN collects a wide assortment of data types from individual patients, including genetic data, medical images, clinical notes, and protein information. This comprehensive picture of a patient enables scientists to see the whole picture and ask more informed, targeted questions.
Exploring New Methodologies
In addition to identifying the NrCAM variant, the team also made another exciting discovery: tiny gene segments known as microexons. These small pieces had never been considered for cancer treatment previously, but now show promise as new targets for immunotherapy treatments in HGG.
Dr. Naqvi and his team created a new system to find more of these unique immunotherapy targets—not just high-grade glioma tumors, but potentially for other cancers and diseases where gene splicing goes awry. He plans to expand these methods by integrating more CBTN data modalities and eventually creating a resource allowing investigators to prioritize targetable splicing variants in any disease context.
While these findings open up promising new avenues, more rigorous preclinical testing and clinical studies are needed to determine if these splicing-based immunotherapy strategies can be safely and effectively translated into patient care.
The Future of Childhood Brain Tumor Treatment
Dr. Naqvi’s path to this work began with a fascination for science and a strong desire to help others. Now, after nearly a decade at Children’s Hospital of Philadelphia, he’s focused on finding better treatments for some of the most vulnerable patients—children with brain cancer.
“Pediatric high-grade gliomas are deadly due to limited therapeutic options and surgical challenges with abysmal survival rates after initial diagnosis,” Dr. Naqvi explains, underscoring the urgent need for new therapeutic targets.
This latest discovery from CBTN scientists, leveraging Kids First data, marks a significant step forward in addressing the challenge posed by childhood brain tumors. And, thanks to this innovative work, there is new momentum in the fight against childhood brain tumors. A widening group of researchers is uncovering smarter, more precise ways to treat these diseases—and helping build a future filled with more options, more discoveries, and most importantly, more hope.
Andrei Thomas-Tikhonenko was the corresponding author of the study, published in Cell Reports. Read it here: https://rebrand.ly/4m3q5rl
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