BRAF and MEK Targeted Therapies in Pediatric Central Nervous System Tumors.

Simple Summary: This review is divided into two parts. The first analyzes the mechanisms of two important cellular pathways that are involved in tumoral proliferation, differentiation, migration, and angiogenesis: RAS/RAF/MEK/MAPK and PI3K/AKT/mTOR. The second part focuses on the currently available experience regarding targeted therapies against the mitogen-activated protein kinase (MAPK) pathway in pediatric CNS tumors, with the hope of offering a practical guide for consultation. BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics. The MAPK mutated pathway in pediatric CNS tumors is the target of numerous drugs, approved or under investigation in ongoing clinical trials. In this review, we describe the main aspects of MAPK and PI3K/AKT/mTOR signaling pathways, with a focus on the alterations commonly involved in tumorigenesis. Furthermore, we reported the main available data about current BRAF and MEK targeted therapies used in pediatric low-grade gliomas (pLLGs), pediatric high-grade gliomas (pHGGs), and other CNS tumors that often present BRAF or MEK mutations. Further molecular stratification and clinical trial design are required for the treatment of pediatric CNS tumors with BRAF and MEK inhibitors. [ABSTRACT FROM AUTHOR]