Targeted therapy for pediatric glioma: RAF(t)ing in the molecular era.

in World journal of pediatrics : WJP by Zhi-Peng Shen, Zhong-Yuan Zhang, Nan Li, Liang Xu, Ye Chen

TLDR

  • This review provides an overview of recent advancements and evolving landscapes of targeted therapeutic strategies and approaches for pediatric gliomas, highlighting multiomics profiling and targeted therapies as promising avenues for more effective and personalized treatment options.

Abstract

Pediatric gliomas are the most frequently occurring central nervous system tumors in children. While targeted therapies have been widely applied in the treatment of many adult cancers, their use in pediatric gliomas has lagged behind. However, recent advances in multiomics profiling of pediatric gliomas, coupled with the approval of inhibitors against Raf serine/threonine kinase (RAF), isocitrate dehydrogenase 1/2 (IDH1/2) and neurotrophic receptor tyrosine kinase (NTRK), have spurred significant progress in this field. In light of these developments, this review aims to provide a comprehensive overview of current advancements and the evolving landscape of targeted therapeutic strategies and approaches for pediatric gliomas. Data analyzed in this study were obtained from the literature from PubMed, as well as other online databases and websites, including ClinicalTrials.gov and the Pediatric Neuro-Oncology Consortium. Based on findings from multiomics profiling, significant insights have been gained into the genetic and molecular landscape of pediatric gliomas, enabling the identification of key mutations and potentially targetable lesions. These advancements provide rationales for the development of more precise treatment strategies and targeted therapies. Recent approvals of targeted therapies and ongoing clinical trials in pediatric gliomas are converging on the targeting of key signaling molecules and metabolic pathways. In the molecular era, targeted therapies offer new hope for more effective and personalized treatment options for pediatric glioma patients. By developing and tailoring treatments to target specific molecular and metabolic vulnerabilities, targeted therapies have the potential to improve the clinical management of pediatric gliomas, ultimately enhancing both the treatment experience and overall prognosis of these patients.

Overview

  • The study aims to provide a comprehensive overview of current advancements and evolving landscapes of targeted therapeutic strategies and approaches for pediatric gliomas.
  • The study highlights recent advances in multiomics profiling of pediatric gliomas and the approval of inhibitors against RAF, IDH1/2, and NTRK, which have spurred significant progress in this field.
  • The study reviews the genetic and molecular landscape of pediatric gliomas, enabling the identification of key mutations and potentially targetable lesions, and provides rationales for the development of more precise treatment strategies and targeted therapies.

Comparative Analysis & Findings

  • Recent advances in multiomics profiling have provided significant insights into the genetic and molecular landscape of pediatric gliomas, enabling the identification of key mutations and potentially targetable lesions.
  • Targeted therapies offer new hope for more effective and personalized treatment options for pediatric glioma patients, as developing and tailoring treatments to target specific molecular and metabolic vulnerabilities can improve treatment outcomes.
  • Recent approvals of targeted therapies and ongoing clinical trials in pediatric gliomas are converging on the targeting of key signaling molecules and metabolic pathways.

Implications and Future Directions

  • Future research should focus on developing and tailoring treatments to target specific molecular and metabolic vulnerabilities, which can improve treatment outcomes and enhance both the treatment experience and overall prognosis of pediatric glioma patients.
  • Studies should continue to explore the genetic and molecular landscape of pediatric gliomas, enabling the identification of key mutations and potentially targetable lesions.
  • Clinical trials should focus on testing targeted therapies in pediatric gliomas and exploring their efficacy and safety in different patient populations.
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