Targeted therapy in pediatric central nervous system tumors: a review from the National Pediatric Cancer Foundation
Authors: Siegel BI, Patil P, Prakash A, Klawinski DM and Hwang EI (2025)
Link: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1504803/full
Background Information:
Brain and spinal cord tumors are, tragically, the top cause of cancer-related deaths in children. Traditional treatments—like surgery, radiation, and high-dose chemo—can sometimes slow things down or shrink tumors, but they come with a heavy cost. The side effects can be brutal, and in many cases, they don’t offer a cure. Over the past decade, though, there’s been a shift in how researchers approach these tumors. As we’ve learned more about the specific genetic and molecular changes that drive pediatric brain cancers, a new treatment path has started to take shape: targeted therapy. Instead of blasting everything in sight, these drugs go after specific faulty proteins or disrupted signaling pathways inside cancer cells. The hope is to treat the tumor more precisely, while sparing healthy brain tissue—something that’s especially critical in growing children. This review paper takes a close look at recent developments in targeted therapies for pediatric central nervous system (CNS) tumors and what they might mean for the future of treatment.
Purpose of the Study:
The main goal of the paper was to take stock of where things stand in the development of molecularly targeted treatments for brain and spinal tumors in children. It offers a snapshot of how scientists are mapping genetic changes—such as alterations in the MAPK and PI3K/mTOR pathways—and matching them with specific drugs that can potentially block those signals. The authors also walked through which targeted therapies have already reached clinical trials, which are still in early stages, and what practical and scientific hurdles remain. In essence, the review aims to help researchers, clinicians, and even families understand what’s working, what’s experimental, and where this line of research might be headed.
Methods and Data Analysis:
Rather than running new experiments, this was a narrative review—meaning the authors pulled together data from existing research papers, clinical trials, and molecular studies. Their focus was mostly on the key pathways that often get disrupted in pediatric CNS tumors. These include the MAPK pathway (especially BRAF mutations and fusions), PI3K/mTOR signaling, and receptor tyrosine kinases like NTRK. The paper goes a step further than just listing drugs: it looks at how therapies are being combined, what strategies are being used to get drugs across the notoriously difficult blood-brain barrier, and how personalized drug screening is being incorporated into care. It also includes summary tables, which break down where each drug stands in terms of testing and approval.
Key Findings and Conclusions:
One area where progress is especially noticeable is in low-grade gliomas, which often involve mutations in the MAPK pathway. Drugs like dabrafenib and trametinib (which target BRAF mutations), as well as larotrectinib and entrectinib (which go after NTRK fusions), have shown meaningful results and even earned FDA approval for certain pediatric cancers. That said, targeted therapy isn’t a silver bullet. Tumors often find ways to adapt. Many patients who respond at first eventually relapse—sometimes quickly—once treatment stops or resistance kicks in. The authors argue that combining therapies might offer a better shot at long-term control, especially when used alongside immunotherapy or more traditional methods. Targeted drugs do have clear advantages—they’re often oral, less toxic, and more manageable than chemotherapy—but they’re not without risks. Long-term impacts on development, cognition, and fertility still aren’t fully understood. And most of the trials conducted so far have involved small numbers of patients, making it tough to draw broad conclusions. Still, the overall message is hopeful: with smarter clinical strategies and more personalized approaches, targeted therapy could play a major role in reshaping how we treat brain and spinal tumors in kids.
Applications & Limitations:
Targeted drugs offer hope for more effective and gentler treatments in kids, reducing hospital stays and side effects compared to traditional chemotherapy. Oral formulations and fewer immune-suppressing effects make them convenient and potentially safer. But challenges remain: tumors often develop resistance, and most trials so far are early-stage with small patient numbers. Novel drug delivery methods are being explored to overcome barriers like the blood-brain barrier, yet long-term side effects—on growth, development, fertility, and cognition—are still unknown. The paper emphasizes the need for smarter clinical strategies, such as combination therapy and personalized treatment trials, to improve outcomes in pediatric CNS tumors.