Innovations in Targeted and Gene Therapy in Pediatric Oncology

Recent innovations in targeted and gene therapy are rapidly reshaping clinical outcomes in pediatric oncology, offering new hope for challenging cases such as pediatric gliomas.

Despite aggressive multimodal treatment, pediatric gliomas remain a clinical challenge, with traditional chemotherapy often failing to achieve sustained disease control. The emergence of targeted therapies strikes at the heart of tumor biology: pediatric gliomas driven by fibroblast growth factor receptor (FGFR) alterations show marked sensitivity to selective inhibitors. Recent findings indicate that in a phase II trial of an FGFR inhibitor in pediatric glioma, 62% of patients (8/13) achieved stable disease for a median duration of 4.8 months, signaling a pivotal shift toward personalized treatment paradigms.

Building on this momentum, the approval of targeted agents for alternative genetic drivers has broadened therapeutic horizons. Pediatric low-grade gliomas harboring the BRAF V600E mutation may benefit from combined BRAF and MEK inhibition: while dabrafenib plus trametinib is FDA-approved for melanoma, its use in pediatric gliomas remains investigational, with early trials reporting an objective response rate of 40% and a median progression-free survival of 9 months.

Parallel advances in gene therapy are informing our understanding of treatment endpoints and immune development. Trials in X-SCID use gene therapy with mild preconditioning to restore T-cell function, underscoring Lentiviral Gene Therapy with Low Dose Busulfan as a pivotal insight, illuminating early immune maturation and offering lessons for broader oncology applications.

Pediatric oncologists should integrate genomic profiling early in diagnostic workflows—as recommended by the NCCN Pediatric Central Nervous System Cancers Guidelines—to identify eligible patients for FGFR-targeted or BRAF-directed therapy and consider gene therapy referrals for immunodeficiencies that unveil immune-oncology intersections. Barriers in access and long-term follow-up data persist, underscoring the need for multicenter collaboration and registries that track late effects and resistance mechanisms. Continued expansion of molecular targets promises to refine early diagnostics and uncover novel intervention points.

Key Takeaways:

• FGFR inhibitors offer stable disease in pediatric gliomas with FGFR alterations.
• Dabrafenib and trametinib expand options for BRAF-mutated gliomas.
• X-SCID gene therapy not only addresses immune deficiencies but also educates about immune system development.